Antinociceptive Effect of a p-Cymene/ß-Cyclodextrin Inclusion Complex in a Murine Cancer Pain Model: Characterization Aided through a Docking Study.

Pain is one of the most prevalent and difficult to manage symptoms in cancer patients, and conventional drugs present a range of adverse reactions. The development of ß-cyclodextrins (ß-CD) complexes has been used to avoid physicochemical and pharmacological limitations due to the lipophilicity of compounds such as p-Cymene (PC), a monoterpene with antinociceptive effects. Our aim was to obtain, characterize, and measure the effect of the complex of p-cymene and ß-cyclodextrin (PC/ß-CD) in a cancer pain model. Initially, molecular docking was performed to predict the viability of complex formation. Afterward, PC/ß-CD was obtained by slurry complexation, characterized by HPLC and NMR. Finally, PC/ß-CD was tested in a Sarcoma 180 (S180)-induced pain model. Molecular docking indicated that the occurrence of interaction between PC and ß-CD is favorable. PC/ß-CD showed complexation efficiency of 82.61%, and NMR demonstrated PC complexation in the ß-CD cavity. In the S180 cancer pain model, PC/ß-CD significantly reduced the mechanical hyperalgesia, spontaneous nociception, and nociception induced by non-noxious palpation at the doses tested (p < 0.05) when compared to vehicle differently from free PC (p > 0.05). Therefore, the complexation of PC in ß-CD was shown to improve the pharmacological effect of the drug as well as reducing the required dose.

Genomics-based higher classification of the species-rich Hairstreaks (Lepidoptera: Lycaenidae: Eumaeini).

We propose a higher classification of the lycaenid hairstreak tribe Eumaeini - one of the youngest and most species-rich butterfly tribes - based on autosome, Lepidopteran Z sex chromosome, and mitochondrial protein-coding genes. The subtribe Neolycaenina Korb is a synonym of Callophryidina Tutt, and subtribe Tmolusina Bálint is a synonym of Strephonotina K. Johnson, Austin, Le Crom, & Salazar. Proposed names are Rhammina Prieto & Busby, new subtribe; Timaetina Busby & Prieto, new subtribe; Atlidina Martins & Duarte, new subtribe; Evenina Faynel & Grishin, new subtribe; Jantheclina Robbins & Faynel, new subtribe; Paiwarriina Lamas & Robbins, new subtribe; Cupatheclina Lamas & Grishin, new subtribe; Parrhasiina Busby & Robbins, new subtribe; Ipideclina Martins & Grishin, new subtribe; and Trichonidina Duarte & Faynel, new subtribe. Phylogenetic results from the autosome and Z sex chromosome analyses are similar. Future analyses of datasets with hundreds of terminal taxa may be more practical time-wise by focussing on the smaller number of sex chromosome sequences (2.6% of nuclear protein-coding sequences). The phylogenetic classification and biological summaries for each subtribe suggest that a variety of factors affected Eumaeini diversification. About a dozen kinds of male secondary sexual organs with frequent evolutionary gains and losses occur in Atlidina, Evenina, and Jantheclina (141 species combined). Females have been shown to use these organs to discriminate between conspecific and non-conspecific males, facilitating sympatry among close relatives. Eumaeina, Rhammina, and Timaetina (140 species combined) are overwhelmingly montane with some evidence for a higher incidence of sympatric diversification. Seven Neotropical lineages in five subtribes invaded the temperate parts of the Nearctic Region with a diversification increase in the Callophryidina (262 species). North American Satyrium and Callophrys then invaded the Palearctic at least once each, with a major species-richness increase in Satyrium. The evolution of litter feeding detritivores within Calycopidina (172 species) resulted in an increase in diversification rate compared with its flower-feeding sister lineage. Atlidina, Strephonotina, Parrhasiina, and Strymonina (562 species combined) each contain a mixture of genera that specialize on one or two caterpillar food plant families and genera that are polyphagous. These would be appropriate subtribes to assess how the breadth of caterpillar food plants and the frequency of host shifts affected diversification.

Evolution of sexual dimorphism and polychromatism in a lineage of tiger moths (Lepidoptera: Erebidae): advancing knowledge of a taxonomically chaotic group.

Pericopina is divided into 36 genera, with the greatest diversity recorded in the Neotropics. Studies on the taxonomy and systematics of pericopines are scarce, and one of the few phylogenetic hypotheses available in the literature places some Afro-Indo-Malayan lineages among the Neotropical representatives. Through a survey of adult morphological characters, we analyzed the phylogenetic relationships in Pericopina including Nyctemera and other Afro-Indo-Malayan genera as putative members of this subtribe. Additionally, we tested the monophyly of Dysschema, a key genus to understanding the evolutionary patterns of the extreme sexual dimorphism and polychromatism in Pericopina. Our cladistic analysis, based on 162 morphological characters, suggests that Pericopina is a polyphyletic group. Xenosoma is the only genus among the Neotropical pericopines related to the Afro-Indo-Malayan species; Scearctia is closely related to Lithosiini, and Pteroodes shows morphological similarities with Phaegopterina. Additionally, Seileria is a new junior subjective synonym of Thyrgis. The monophyly of Dysschema is supported only if the monotypic genera Myserla and Are are included. These are herein designated new synonyms of Dysschema. Our findings suggest that intersexual polychromatism and intersexual polymorphism for wing characters have arisen multiple times in the evolutionary history of Pericopina. Intersexual polychromatism is also widely distributed within Dysschema, perhaps representing a derived feature with multiple origins in the genus.

Visible-Light-Mediated Strategies for the Preparation of Oxime Ethers Derived from O-H Insertions of Oximes into Aryldiazoacetates.

Two visible-light-mediated O-H insertion protocols involving oximes and aryldiazoacetates leading to different products depending on the solvent employed are reported. In DCM, direct O-H insertion takes place. In THF, there is the additional incorporation of the ring-opened form of this solvent into the structure of the product. These metal-free protocols are mild and tolerant to air and moisture. The preparation of an acaricide has been developed as an example of synthetic application.

Reduced cutaneous inflammation associated with antioxidant action after topical application of the aqueous extract of Annona muricata leaves.

Annona muricata L. is used in folk medicine for treatment of diseases related to inflammatory and oxidative processes. This study investigated the effect of the aqueous extract of A. muricata leaves (AEAM) on TPA-induced ear inflammation and antioxidant capacity, both in vitro and in vivo. The in vitro antioxidant capacity of AEAM was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing/antioxidant power (FRAP) and lipoperoxidation assays. Cytotoxicity and reactive oxygen species (ROS) release were evaluated in the L929 fibroblasts. Swiss mice were submitted to TPA application and were topically treated with AEAM (0.3, 1 or 3 mg/ear). After 6 h, inflammatory and oxidative parameters were evaluated. Quercetin 3-glucoside, rutin, chlorogenic acid, catechin and gallic acid were identified in AEAM. It also presented antioxidant activity in all in vitro assays used. Incubation with AEAM did not cause cell cytotoxicity but reduced ROS release from fibroblasts. Compared with the control group, treatment with AEAM significantly reduced ear oedema and mieloperoxidase activity in inflamed ears, as well as histological parameters of inflammation. These results were associated with the reduction of total hydroperoxides and modulation of catalase, but not superoxide dismutase activity. These findings show the anti-inflammatory effect of AEAM is associated with antioxidant capacity.

Differential Diagnosis Between Venomous (Bothrops jararaca, Serpentes, Viperidae) and "Nonvenomous" (Philodryas olfersii, Serpentes, Dipsadidae) Snakebites: Is It Always Possible?

Bites of "nonvenomous" snakes can sometimes be mistaken for the bites of venomous snakes. As an example of this confusion, this report describes confirmed bites by Philodryas olfersii and Bothrops jararaca. In the first case, a 55-y-old man with a history of controlled hypertension was bitten on his right forearm by P olfersii. Physical examination revealed extensive edema, erythema, and widespread ecchymoses throughout his right upper limb. Laboratory tests indicated leukocytosis and high D-dimer levels, but normal coagulation, suggestive of a resolved recent coagulopathy. He received only supportive treatment. In the second case, a healthy 35-y-old man was bitten by B jararaca. Although the anatomic region of the bite and the results of physical examination were similar to those in the first case, laboratory tests showed mild coagulopathy, leukocytosis, and high D-dimer levels. The patient was treated with antivenom. In both cases, the 20-min whole blood clotting test results were normal. Patients bitten by P olfersii may present with local symptoms resembling B jararaca envenomation. Without snake identification and the detection of venom-induced consumption coagulopathy, especially in places where the 20-min whole blood clotting test is the only clotting test available, it is almost impossible to establish an accurate and safe differential diagnosis. In this context, the best alternative is to take the risk of prescribing antivenom for a possible P olfersii bite rather than failing to do so for a real Bothrops bite. Late treatment for Bothrops bite can result in severe complications and sequelae.

Altitudinal variation in butterfly community associated with climate and vegetation.

Elevation creates a variety of physical conditions in a relatively short distance, which makes mountains suitable for studying the effects of climate change on biodiversity. We investigated the importance of climate and vegetation for the distribution of butterflies from 800 to 1400 m elevation. We sampled butterflies, and woody and rosette plants and measured air temperature and humidity, wind speed and gust, and solar radiation. We partitioned diversity to assess the processes underlying community shifts across altitudes - species loss versus replacement. We assessed the strength of the association among butterfly, vegetation, and climate. Butterfly richness and abundance decreased with altitude, and species composition changed along the elevation. Changes in butterfly composition with altitude were mainly through species replacement and by abundance increases in some species being compensated by decreases in others. Since the floristic diversity decreased with altitude due to soil conditions, and butterflies are closely related to their host plants, this could explain species replacement with altitude. Overall, we found a stronger association of butterfly community with vegetation than climate, but plant community and climate were also strongly associated between them. Butterfly richness was more strongly associated with plant richness than with temperature, while the reverse was true for butterfly abundance, which was more strongly associated with temperature than with plant richness. We must consider the complementary roles of resource and conditions in species distribution.

Hairstreak butterflies (Lepidoptera, Lycaenidae) and evolution of their male secondary sexual organs.

Hairstreak butterflies in the Atlides Section of the Eumaeini are biologically notable for a diverse array of male secondary sexual organs. A "species recognition" hypothesis postulates that females use these organs to choose between conspecific and non-conspecific males, thereby promoting reproductive isolation. Alternately, a "sexual selection" hypothesis posits that females use these organs to choose among conspecific males. These hypotheses need not be mutually exclusive but make different predictions about the evolutionary gain and loss of male secondary sexual organs. We analysed most of the Atlides Section (Theclinae, Eumaeini) phylogenetically. Sister lineages were sympatric at 22 of 37 nodes. Nine evolutionary gains occurred in lineages that were sympatric with their phylogenetic sister, and one occurred in a lineage that was allopatric/parapatric with its sister. By contrast, seven of ten evolutionary losses occurred in lineages that were allopatric/parapatric with their sisters. These results are significantly different from those predicted by a sexual selection hypothesis. We conclude that male secondary sexual organs in the Atlides Section function primarily for species recognition and thereby promote sympatric diversification.

Description of a second known Liotyphlops caissara specimen (Serpentes: Anomalepididae).

We recorded a second specimen of the poorly known insular blind snake Liotyphlops caissara. This new specimen expands the morphological variation of the number of dorsal scales in the genus Liotyphlops to 296 (vs. 304 in L. wilderi) and, considering the fact that the holotype of this species was destroyed, the present specimen represents the only available L. caissara individual in zoological collections. Also, this new record constitutes the first out of type locality and expands the distribution of the species in about 40 km to the northeastern. According to IUCN criteria (B1a, b [iii]), we suggest that L. caissara be included in the "Endangered" category, since it occurs in only two insular locations and exhibits an occurrence extension of <5,000 km² (about 355 km2).

Saturniid moths (Lepidoptera: Bombycoidea) from an Atlantic Rain Forest fragment in southeastern Brazil.

The light-attracted silk moths (Lepidoptera: Saturniidae) of the Boraceia Biological Station in the municipality of Salesópolis, state of São Paulo, southeastern Brazil have been sampled over more than seven decades (1942-2013). A total of 6,288 individuals (including a gynandromorph) belonging to five subfamilies, 46 genera and 133 species were identified. Hemileucinae was the most abundant and speciesrich subfamily, followed by Ceratocampinae, Arsenurinae, Saturniinae, and Oxyteninae. Hylesia Hübner, Automeris Hübner, and Dirphiopsis Bouvier (Hemileucinae) were the dominant genera in abundance and species richness. Only Automeris illustris (Walker), Gamelia remissoides Lemaire, and Hidripa paranensis (Bouvier) (Hemileucinae) were recorded in all months of sampling. Hylesia metapyrrha (Walker) was the most abundant saturniid species recorded at the station, with 375 specimens, followed by Hylesia oratex Dyar with 265 specimens, Dirphia muscosa Schaus with 261 specimens (all Hemileucinae); Copaxa canella Walker (Saturniinae) with 232 specimens, and Lonomia cf. obliqua Walker (Hemileucinae) with 106 specimens. Fifteen additional species were each represented by more than 100 specimens. The importance of the Boraceia Biological Station to the maintenance of the saturniid moth diversity in the Atlantic Forest is discussed.

An Aminocatalyzed Michael Addition/Iron-Mediated Decarboxylative Cyclization Sequence for the Preparation of 2,3,4,6-Tetrasubstituted Pyridines: Scope and Mechanistic Insights.

A novel, scalable strategy for the preparation of 2,3,4,6-tetrasubstituted pyridines is described. This protocol has two steps: an aminocatalyzed addition of ketones to alkylidene isoxazol-5-ones, followed by an iron-mediated decarboxylative cyclization event. Mechanistic insights for both steps are provided based on HRMS-ESI(+) studies.

Essential oil from fruit of Xylopia langsdorffiana: antitumour activity and toxicity.

CONTEXT: The genus Xylopia L. (Annonaceae) includes aromatic plants that have both nutritional and medicinal uses. Essential oils of Xylopia species have antitumour effects. However, the efficacy of the essential oil from the fruit of Xylopia langsdorffiana St. Hil & Tul. (EOX) has not been examined. OBJECTIVE: EOX was evaluated to determine its chemical composition, antitumour activity and toxicity. MATERIALS AND METHODS: EOX was obtained from fresh fruits of X. langsdorffiana subjected to hydrodistillation, and gas chromatography-mass spectrometry was used to characterize the chemical composition of EOX. The toxicity of EOX was evaluated using haemolysis, acute toxicity and micronucleus assays. The in vitro antitumour activity of EOX was investigated using the sulforhodamine B assay. The sarcoma 180 murine tumour model was used to evaluate the in vivo antitumour activity and toxicity of EOX (50 and 100 mg/kg) after 7 d of treatment. RESULTS: The major components of EOX were α-pinene (34.57%) and limonene (31.75%). The HC50 (concentration producing 50% haemolysis) was 293.6 µg/ml. EOX showed greater selectivity for the leukaemia cell line K562, with total growth inhibition (TGI) (concentration producing TGI) of 1.8 µg/ml, and for multidrug-resistant ovarian tumour cell line NCI/ADR-RES (TGI of 45.4 µg/ml). The LD50 was approximately 351.09 mg/kg. At doses of 50 and 100 mg/kg, EOX inhibited the in vivo growth of sarcoma 180 by 38.67 and 54.32%, respectively. EOX displayed minor hepatic alterations characteristic of acute hepatitis and induced no genotoxicity. CONCLUSION: EOX showed in vitro and in vivo antitumour activity and low toxicity, which warrants further pharmacological studies.

Larval biology of anthophagous Eumaeini (Lepidoptera: Lycaenidae, Theclinae) in the cerrado of central Brazil.

The biology and morphology of the early stages of 22 species of Eumaeini (Lepidoptera: Lycaenidae, Theclinae) are presented. Observations were collected through the inspection of inflorescences in the field and the rearing of 214 larvae in laboratory. Allosmaitia strophius (Godart) associated with Malpighiaceae species and the polyphagous Strymon mulucha (Hewitson) were the most frequently collected species. Detritivory was observed in two species, Electrostrymon endymion (F.) and Kisutam syllis (Godman & Salvin), and myrmecophily in four other species, A. strophius, Ministrymon azia (Hewitson), Parrhasius polibetes (Stoll), and S. mulucha. Cannibalism was observed in A. strophius; in addition, the pupa of this and of three other species produced audible sounds. Paiwarria aphaca (Hewitson) was highlighted because of the great difference observed between its first and last instars, as well as the marked difference between that species and the larvae of Paiwarria umbratus (Geyer) documented in Costa Rica. Larvae of Calycopis mimas (Godman & Salvin) displayed "bungee jumping" behavior when stimulated. Parasitoids (Diptera, Hymenoptera) attacked 21 larvae of eight species, A. strophius, K. syllis, M. azia, Pai. aphaca, P. polibetes, Rekoa marius (Lucas), S. mulucha, and Tmolus venustus (H.H. Druce). Illustrations of immatures and parasitoids are provided.

Hemoperitoneum after a Bothrops snakebite: Case report.

Snakebites are frequent in tropical countries. Brazil has an average of 27,000 cases per year, with a fatality rate of 0.5%, and the Bothrops genus is the most common causative agent, accounting for about 70-90% of the accidents. This report describes a case of human envenomation by a juvenile Bothrops jararaca snake in São Paulo, Brazil, in a 71 years-old man, previously healthy. He presented a life-threatening envenomation, which developed to severe hypotension, acute kidney injury and extensive peritoneal hemorrhage. The hemoperitoneum was diagnosed due to persistent hypotension associated with anemia, pain and gastrointestinal complaints. Abdominal Computed Tomography scans showed a moderate to large amount of presumable hematic material inside the abdominal cavity, predominantly in the perihepatic and perisplenic spaces. The intra-abdominal hemorrhage was not surgically addressed, and the patient was discharged 5 days after hospitalization, with the progressive absorption of the hemoperitoneum. Systemic bleeding is one of the complications and main causes of death in Bothrops envenomations. Acute peritoneal hemorrhage is one of these serious complications that must be carefully addressed since its management must take into account the risk of bleeding caused by toxins that affect hemostasis. The case described highlights the importance of early diagnosis and adequate management of this potentially fatal complication in snakebites.

Endoscopic Ventricular Lavage in Pediatric Pyogenic Cerebral Ventriculitis Associated with Shunt: Outcomes and Technical Notes.

OBJECTIVE: Pyogenic cerebral ventriculitis (PCV) is a rare infectious entity characterized by a potent inflammatory reaction of the ventricular ependyma, which in most cases leads to death. We aim to present the technical note and protocol, based on our center's 10-year experience of the use of endoscopic ventricular lavage (EVL) in pediatric patients with PCV and ventricular peritoneal shunt. METHODS: For this study, all pediatric patients (<16 years) with VP shunts and PCV who were treated with EVL between January 2012 and January 2022 were included. RESULTS: Thirty-four pediatric patients with ventriculitis were analyzed. The median age was 6 years, with 61.7% being male. Most consultations occurred on Day 2 of symptoms. Fever (38.2%) and altered consciousness (26.5%) were the most common initial symptoms. Early ventriculitis was observed in 67.7% of patients. Pathogen identification in the initial cerebrospinal fluid sample was 70.6%, while samples from ventricular peritoneal shunt yielded 23.53% and catheter culture 79.4%. Gram-positive bacteria, mainly S.epidermidis (44.1%), was the most commonly isolated agent. EVL was performed in 73.5% on the second or third day. Reinfection occurred in 23.5%, and 26.5% of patients died. Concordance analysis showed 85.3% agreement between LP and catheter tip samples. Functionality improved, with 55.88% achieving a Lansky score of 90. Early ventriculitis was associated with better Lansky scores. CONCLUSION: EVL can be a useful tool in the management of PCV in cases with VP shunts. Our study suggests a higher chance of isolating an infection-causing germ in the catheter tip culture specimen compared to the cerebrospinal fluid culture. However, future studies with a larger number of patients, or multicentric studies are required for further analysis.

Resting state networks in patients with acute disorders of consciousness after severe traumatic brain injury.

OBJECTIVES: This study aims to describe resting state networks (RSN) in patients with disorders of consciousness (DOC)s after acute severe traumatic brain injury (TBI). METHODS: Adult patients with TBI with a GCS score <8 who remained in a coma, minimally conscious state (MCS), or unresponsive wakefulness syndrome (UWS), between 2017 and 2020 were included. Blood-oxygen-level dependent imaging was performed to compare their RSN with 10 healthy volunteers. RESULTS: Of a total of 293 patients evaluated, only 13 patients were included according to inclusion criteria: 7 in coma (54%), 2 in MCS (15%), and 4 (31%) had an UWS. RSN analysis showed that the default mode network (DMN) was present and symmetric in 6 patients (46%), absent in 1 (8%), and asymmetric in 6 (46%). The executive control network (ECN) was present in all patients but was asymmetric in 3 (23%). The right ECN was absent in 2 patients (15%) and the left ECN in 1 (7%). The medial visual network was present in 11 (85%) patients. Finally, the cerebellar network was symmetric in 8 patients (62%), asymmetric in 1 (8%), and absent in 4 (30%). CONCLUSIONS: A substantial impairment in activation of RSN is demonstrated in patients with DOC after severe TBI in comparison with healthy subjects. Three patterns of activation were found: normal/complete activation, 2) asymmetric activation or partially absent, and 3) absent activation.

Study of the pollen type in Neotropical hawkmoths (Lepidoptera: Sphingidae: Macroglossinae) collected in the Brazilian Atlantic Forest.

We recorded 14 pollen types belonging to 12 families of angiosperms. Pera (Peraceae) pollen type was found in all genera and was the most abundant. Our results suggest low specificity in the choice of flowers; thus, Sphingids with either short or long proboscises visited flowers of the same species.

A comparative study of COVID-19 transcriptional signatures between clinical samples and preclinical cell models in the search for disease master regulators and drug repositioning candidates.

Coronavirus disease 2019 (COVID-19) is an acute viral disease with millions of cases worldwide. Although the number of daily new cases and deaths has been dropping, there is still a need for therapeutic alternatives to deal with severe cases. A promising strategy to prospect new therapeutic candidates is to investigate the regulatory mechanisms involved in COVID-19 progression using integrated transcriptomics approaches. In this work, we aimed to identify COVID-19 Master Regulators (MRs) using a series of publicly available gene expression datasets of lung tissue from patients which developed the severe form of the disease. We were able to identify a set of six potential COVID-19 MRs related to its severe form, namely TAL1, TEAD4, EPAS1, ATOH8, ERG, and ARNTL2. In addition, using the Connectivity Map drug repositioning approach, we identified 52 different drugs which could be used to revert the disease signature, thus being candidates for the design of novel clinical treatments. Furthermore, we compared the identified signature and drugs with the ones obtained from the analysis of nasopharyngeal swab samples from infected patients and preclinical cell models. This comparison showed significant similarities between them, although also revealing some limitations on the overlap between clinical and preclinical data in COVID-19, highlighting the need for careful selection of the best model for each disease stage.

Occurrence and distribution of Panstrongylus megistus (Burmeister, 1835) (Hemiptera, Reduviidae) in a metropolitan area of Southern Brazil.

Two triatomine genera (Panstrongylus and Triatoma) have essentially been recorded in Rio Grande do Sul State, Brazil. Panstrongylus megistus should be highlighted since this species is one of the main vectors of Trypanosoma cruzi in Brazil, due to its wide geographical distribution and the high susceptibility to this protozoan. This study aimed to present not only the occurrence and distribution of P. megistus in the Porto Alegre city's metropolitan area (PAMA), Rio Grande do Sul State, Brazil, but also the rates of T. cruzi infection, from 2009 to 2020. The PAMA, which comprises 34 cities and 4.4 million habitants, extends across the transition area in two biomes - Pampa and Mata Atlantica - found in the state. Results showed that P. megistus was recorded in 76.5% of cities (i.e., 26 out of 34), mainly in Porto Alegre city, where the vector was found in 11 out of the 12 years that were monitored. Three hundred and nineteen specimens were captured. Two hundred and sixty-seven specimens (83.7%) were located intradomicile (p < 0.0001), while 52.3% positivity for T. cruzi was found. Thus, P. megistus is important in the PAMA, because it invades and colonizes the households. Moreover, the high rates of T. cruzi infection have drawn attention.