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ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.
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BACKGROUND: Differences in definitions and operational diagnoses for sarcopenia create difficulties in understanding the epidemiology of the disease. We examined the prevalences of sarcopenia using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) consensuses and analyzed their level of agreement in patients receiving hemodialysis. METHODS: Data from the SARCopenia trajectories and associations with clinical outcomes in patients receiving hemodialysis (SARC-HD) multicenter study in Brazil were analyzed. Muscle strength was assessed using handgrip strength, muscle mass by calf circumference, and physical performance by the 4-m gait speed test. Sarcopenia was diagnosed according to both the EWGSOP2 (low muscle strength plus low muscle mass) and the SDOC (low muscle strength plus low physical performance). The Cohen kappa statistic was used to determine the level of agreement between the consensuses. RESULTS: 838 patients (57.8 ± 15.0 years; 61% men) from 19 dialysis units were included. We found similar prevalences of sarcopenia between the consensuses (EWGSOP2, n = 128, 15.3%; SDOC, n = 105, 12.5%) but with weak agreement (50 of 233 patients, 21.5%; κ = 0.34, 95% CI 0.25-0.43). Agreement was also weak within age categories (≥60 years, κ = 0.34; <60 years, κ = 0.15; both P < 0.001). Of the 51 patients diagnosed by the EWGSOP2 criterion as having severe sarcopenia, all but 1 (98.0%) met the SDOC criterion for sarcopenia (κ = 0.61, 95% CI 0.52-0.70). Low muscle strength was more frequently diagnosed using the SDOC than with the EWGSOP2 (52.3% vs 25.9%). CONCLUSION: We found a weak agreement between the EWGSOP2 and SDOC consensuses for the diagnosis of sarcopenia in patients receiving hemodialysis. Although still weak, agreement was marginally better for older patients. These findings highlight the importance of a global and standardized conceptual diagnosis of sarcopenia.
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American tegumentary leishmaniasis (ATL) is highly endemic in the Amazon basin and occurs in all South American countries, except Chile and Uruguay. Most Brazilian ATL cases are due to Leishmania (Viannia) braziliensis, however other neglected Amazonian species are being increasingly reported. They belong to the subgenus L. (Viannia) and information on suitable models to understand immunopathology are scarce. Here, we explored the use of the golden hamster Mesocricetus auratus and its macrophages as a model for L. (Viannia) species. We also studied the interaction of parasite glycoconjugates (LPGs and GIPLs) in murine macrophages. The following strains were used: L. (V.) braziliensis (MHOM/BR/2001/BA788), L. (V.) guyanensis (MHOM/BR/85/M9945), L. (V.) shawi (MHOM/BR/96/M15789), L. (V.) lindenbergi (MHOM/BR/98/M15733) and L. (V.) naiffi (MDAS/BR/79/M5533). In vivo infections were initiated by injecting parasites into the footpad and were followed up at 20- and 40-days PI. Parasites were mixed with salivary gland extract (SGE) from wild-captured Nyssomyia neivai prior to in vivo infections. Animals were euthanized for histopathological evaluation of the footpads, spleen, and liver. The parasite burden was evaluated in the skin and draining lymph nodes. In vitro infections used resident peritoneal macrophages and THP-1 monocytes infected with all species using a MOI (1:10). For biochemical studies, glycoconjugates (LPGs and GIPLs) were extracted, purified, and biochemically characterized using fluorophore-assisted carbohydrate electrophoresis (FACE). They were functionally evaluated after incubation with macrophages from C57BL/6 mice and knockouts (TLR2-/- and TLR4-/-) for nitric oxide (NO) and cytokine/chemokine production. All species, except L. (V.) guyanensis, failed to generate evident macroscopic lesions 40 days PI. The L. (V.) guyanensis lesions were swollen but did not ulcerate and microscopically were characterized by an intense inflammatory exudate. Despite the fact the other species did not produce visible skin lesions there was no or mild pro-inflammatory infiltration at the inoculation site and parasites survived in the hamster skin/lymph nodes and even visceralized. Although none of the species caused severe disease in the hamster, they differentially infected peritoneal macrophages in vitro. LPGs and GIPLs were able to differentially trigger NO and cytokine production via TLR2/TLR4 and TLR4, respectively. The presence of a sidechain in L. (V.) lainsoni LPG (type II) may be responsible for its higher proinflammatory activity. After Principal Component analyses using all phenotypic features, the clustering of L. (V.) lainsoni was separated from all the other L. (Viannia) species. We conclude that M. auratus was a suitable in vivo model for at least four dermotropic L. (Viannia) species. However, in vitro studies using peritoneal cells are a suitable alternative for understanding interactions of the six L. (Viannia) species used here. LRV1 presence was found in L. (V.) guyanensis and L. (V.) shawi with no apparent correlation with virulence in vitro and in vivo. Finally, parasite glycoconjugates were able to functionally trigger various innate immune responses in murine macrophages via TLRs consistent with their inflammatory profile in vivo.
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Modelos Animales de Enfermedad , Leishmania , Macrófagos , Mesocricetus , Animales , Macrófagos/parasitología , Macrófagos/inmunología , Ratones , Leishmania/patogenicidad , Cricetinae , Virulencia , Femenino , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/patología , Leishmaniasis Cutánea/inmunología , Glicoconjugados , MasculinoRESUMEN
A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.
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Trasplante de Córnea , Mitomicina , Humanos , Mitomicina/uso terapéutico , Trasplante de Córnea/métodos , Enfermedades de la Córnea/cirugía , Enfermedades de la Córnea/tratamiento farmacológico , Neoplasias del Ojo/cirugía , Neoplasias del Ojo/tratamiento farmacológico , Neoplasias del Ojo/patología , Resultado del Tratamiento , Masculino , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Antibióticos Antineoplásicos/uso terapéuticoRESUMEN
This systematic review evaluated the effect of different hydrofluoric acid (HF) etching regimens and a self-etch ceramic primer (SECP) on the flexural strength (FS) and fatigue failure load (FFL) of glass-ceramic materials.The identification of relevant studies was conducted by two authors in five databases: PubMED, Scopus, Web Of Science, LILACS and Virtual Health Library (BVS) until July 2022 with no year limit. The analysis was conducted in RevMan 5.4.1 Software (Cochrane Collaboration) using Random effect model at 5 %. The risk of bias of the included studies were assessed. From the 5349 articles identified, 34 were included for quantitative analysis. Meta-analysis showed that for predominantly glassy ceramics, etching with HF 5 % had no significant impact on FS, however, HF acid etching with concentrations greater than 5 % negatively impacted FS. For lithium disilicate glass-ceramics (LDGC) HF acid etching, negatively influenced FS, while increasing the FFL. HF etching negatively affected FS of hybrid ceramics. The self-etch ceramic primer and HF acid etching showed a similar impact on FFL and FS. This meta-analysis indicates that the impact of SECP and HF acid etching on the mechanical behavior of glass ceramics is material-dependent.
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Persistent double dorsal aorta is an extremely rare congenital anomaly, with only 13 cases published to date. The objective of this study is to present this embryological variant as observed in the abdominal aorta of a patient. The anatomical description was written up on the basis of a review of electronic medical records and imaging exams. The patient in this case was an elderly 79-year-old man who presented at emergency with pain at rest in the left lower limb. He was admitted and laboratory tests and imaging exams were ordered. The variation was an imaging finding observed on angiotomography, consisting of complete separation of the abdominal aorta into two portions - a ventral and a dorsal, with different calibers - at the level of the third lumbar vertebra. There was also an anomalous origin of the inferior mesenteric artery.
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BACKGROUND: Rehabilitation in the anterior region requires specific conditions for success, such as the presence of papilla, emergence profile, and balance between pink and white esthetic. OBJECTIVES: This systematic review aimed to evaluate the esthetic risk associated with immediate implant placement with immediate restoration in the anterior superior area, where the facial bone plate may be absent or deficient. MATERIAL AND METHODS: The search was done in PubMed, Embase, Cochrane, Lilacs, Scopus, Scielo, and Google Scholar databases. The investigation involved clinical studies and observational studies published between January 2012 and July 2023. Studies were excluded if there was less than 12-month follow-up, no immediate restoration or facial defect, heavy smokers, or systemic disease. The risk of bias was assessed using the ROBINS-I and Modified-Cochrane RoB tools. RESULTS: Twelve studies were included in this systematic review. The thinner the facial plate, the higher the alveolus's risk of gingival recession or shrinkage. There was an increased interproximal recession when the thin phenotype was associated with flap surgery. An increase in pink esthetic score (PES) was reached when immediate implant placement (IIP) and immediate restoration were done. Soft tissue augmentation achieved more gingival-level stability. Regardless of the initial phenotype, an esthetic outcome was delivered. The risk of bias was high in 1 study and moderate in 3 studies. CONCLUSION: It is possible to conclude that esthetic results and increased final PES or patient satisfaction index in IIP treatments associated with immediate restoration could be obtained even in buccal bone wall defects or gingival recession, regardless of their extension.
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Estética Dental , Carga Inmediata del Implante Dental , Humanos , Huesos Faciales/cirugía , Carga Inmediata del Implante Dental/métodosRESUMEN
Resumo A aorta dorsal dupla persistente é uma anomalia congênita extremamente rara, com apenas 13 casos publicados até o presente momento. Este estudo tem como objetivo apresentar a variação embriológica observada em aorta abdominal do paciente. A descrição anatômica foi realizada a partir da revisão de prontuário eletrônico e exames de imagem. Desta forma, o presente caso refere-se a um paciente idoso de 79 anos admitido em atendimento hospitalar por queixa de dor em membro inferior esquerdo ao repouso. Foi solicitada a internação do mesmo, assim como exames laboratoriais e de imagem. Obtida como um achado de imagem a partir de angiotomografia, a variação consiste na completa separação em duas porções: uma ventral e outra dorsal, de calibres diferentes, da aorta abdominal, ao nível da terceira vértebra lombar. Isso ocorre em conjunto com a origem anômala da artéria mesentérica inferior.
Abstract Persistent double dorsal aorta is an extremely rare congenital anomaly, with only 13 cases published to date. The objective of this study is to present this embryological variant as observed in the abdominal aorta of a patient. The anatomical description was written up on the basis of a review of electronic medical records and imaging exams. The patient in this case was an elderly 79-year-old man who presented at emergency with pain at rest in the left lower limb. He was admitted and laboratory tests and imaging exams were ordered. The variation was an imaging finding observed on angiotomography, consisting of complete separation of the abdominal aorta into two portions - a ventral and a dorsal, with different calibers - at the level of the third lumbar vertebra. There was also an anomalous origin of the inferior mesenteric artery.
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Despite decades of research devoted to finding a vaccine against leishmaniasis, we are still lacking a safe and effective vaccine for humans. Given this scenario, the search for a new prophylaxis alternative for controlling leishmaniasis should be a global priority. Inspired by leishmanization-a first generation vaccine strategy where live L. major parasites are inoculated in the skin to protect against reinfection-live-attenuated Leishmania vaccine candidates are promising alternatives due to their robust elicited protective immune response. In addition, they do not cause disease and could provide long-term protection upon challenge with a virulent strain. The discovery of a precise and easy way to perform CRISPR/Cas-based gene editing allowed the selection of safer null mutant live-attenuated Leishmania parasites obtained by gene disruption. Here, we revisited molecular targets associated with the selection of live-attenuated vaccinal strains, discussing their function, their limiting factors and the ideal candidate for the next generation of genetically engineered live-attenuated Leishmania vaccines to control leishmaniasis.
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Polygala boliviensis is found in the Brazilian semiarid region. This specie is little chemically and biologically studied. Polygala spp. have different metabolites, especially coumarins. Studies indicate that coumarins have antimalarial potential, denoting the importance of researching new active compounds from plants, since the resistance of Plasmodium strains to conventional therapy has increased. The present study aimed to evaluate the antiplasmodial activity of auraptene and poligalen against a chloroquine-resistant strain of Plasmodium falciparum. Coumarins were isolated from P. boliviensis by open column chromatography and identified by Nuclear Magnetic Resonance Spectroscopy. A cytotoxicity assay was carried out using MTT test, and the in vitro antiplasmodial activity was evaluated using the W2 strain. The antiplasmodial activity results found were IC50=0.171 ± 0.016 for auraptene and 0.164 ± 0.012 for poligalen; the selectivity indexes were 78.71 and 609.76, respectively. Inverse virtual screening in the BRAMMT database by OCTOPUS 1.2 was applied to coumarins to find potential P. falciparum targets and showed higher affinity energy of auraptene for purine nucleoside phosphorylase (PfPNP) and of poligalen for dihydroorotate dehydrogenase (PfDHODH). Molecular Dynamics studies (MD and MM-GBSA) approach were applied to calculate binding energies against selected P. falciparum targets and showed that all coumarins were stable at the binding site during simulations. Furthermore, energies were favorable for complexation. This is the first report of auraptene in P. boliviensis species and of in vitro antiplasmodial activity of auraptene and poligalen. In silico studies indicated that the mechanism of action of coumarins is the inhibition of PfPNP and PfDHODH.Communicated by Ramaswamy H. Sarma.
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Antimaláricos , Plasmodium , Polygala , Antimaláricos/farmacología , Antimaláricos/química , Plasmodium falciparum , Extractos Vegetales/química , Cumarinas/farmacologíaRESUMEN
The aim of the present study is to describe the skin morphology and morphometry of the giant anteater (M. tridactyla), based on comparative analysis applied to skin segments from central metacarpal torus (palmar pad), dorsal thorax, ventral cervical, ventral abdomen, medial carpal and nasal regions. In order to do so, eight adult specimens of M. tridactyla were used for macroscopic studies and four for microscopic assessments. Microscopy was used to assess fur general features that were macroscopically assessed through visual analysis. Fragments (2.0cm²) were collected from the selected regions for microscopic studies. Samples were fixed on McDowell solution, processed through routine histology techniques and subjected to semi-serial cuts (5 µm). The cuts were stained in HE, Alcian blue and periodic acid Schiff. General morphology of different skin layers was described, as well as their architecture and composition; mesoscopy of the epidermis, dermis and stratum corneum was also carried out. There was difference in skin morphometry between males and females, and between different skin regions in the same animal, based on the statistical evaluation of the recorded values. All epidermis layers were assessed for the selected regions. Dermis encompassed surface and deep layers; it presented sweat and sebaceous glands, as well as hair follicles. Findings also allowed reporting that epidermis components are easily identified given its thickness, and the large amount of sweat glands in it it contrasts its physiological features.(AU)
O objetivo deste estudo foi descrever a morfologia e morfometria da pele do Tamanduá-bandeira (M. tridactyla), mediante a análise comparativa de segmentos cutâneos das regiões central do toro metacarpal (coxim palmar), dorsal do tórax, cervical ventral, ventral do abdome, medial do carpo e nasal. Para tanto, foram utilizados oito exemplares adultos de M. tri-dactyla para o estudo macroscópico, e quatro destes para o estudo microscópico. Macroscopicamente estudou-se, por meio de análise visual, as características gerais do pelo e pelagem. Para o estudo microscópico, foram coletados fragmentos de 2,0 cm2 das áreas selecionadas. As amostras foram fixadas em solução de McDowell, processadas pelas técnicas rotineiras de his-tologia e submetidas a cortes semi-seriados de 5 µm. Os cortes foram corados com HE, azul de Alcian e ácido periódico de Schiff. Descreveu-se a morfologia geral, a arquitetura e a composição das diferentes camadas da pele e ainda realizou-se a mesoscopia da epiderme, derme e estrato córneo. De acordo com a avaliação estatística dos valores obtidos, houve diferença na morfometria cutânea entre machos e fêmeas, e entre as diferentes regiões cutâneas de um mesmo animal. Nas regiões estu-dadas observou-se todas as camadas da epiderme. A derme compôs-se das camadas superficial e profunda, apresentado glân-dulas sudoríferas e sebáceas e folículos pilosos. Dentre os achados também pode-se relatar que os componentes da epiderme são facilmente identificáveis pela sua maior espessura, além da grande quantidade de glândulas sudoríferas presentes, o que contrasta com suas características fisiológicas.(AU)
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Animales , Fenómenos Fisiológicos de la Piel , Vermilingua/anatomía & histologíaRESUMEN
This study aimed to describe the brain base arteries of the Myrmecophaga tridactyla using ten cadavers of adults from this species, including five male and five female specimens. The arterial vascular bed was perfused via the thoracic aorta with a dyed natural latex solution, and the animals were fixed and preserved with a 10% formaldehyde buffered solution. The encephala were removed, and their vessels dissected. Basilar artery formation occurred by anastomosis of the thick ventral spinal artery with vertebral arteries. The basilar artery formed two arterial islands and gave bulbar and pontine branches, and cranial, middle, and caudal cerebellar arteries and ended by forking into its terminal branches, the caudal communicating arteries. The blood supply of the encephalon derived solely from the vertebrobasilar system, and the arterial circle of the brain was closed caudally and rostrally. The absence of participation of internal carotid arteries in encephalon irrigation, the island formations by the basilar artery, and the fusiform shape of the arterial circle of the brain are peculiar characteristics of the vascular anatomy of the brain base of M. tridactyla.
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Xenarthra , Cerebro/anatomía & histología , VermilinguaRESUMEN
In this study, B. cereus was detected in dialysis fluids within international parameters (ultrapure - maximum limit of 0.1 CFU/mL for heterotrophic bacteria count) by analyzing the pellet obtained through the centrifugation method. We also investigated the ability of the B. cereus isolate to form a biofilm at different temperatures, the production of virulence factors, and the susceptibility to commercial antimicrobial agents. This study demonstrated a high ability of B. cereus to persist in the hemodialysis system, which can be explained by its broad ability to produce a biofilm at 25 °C, its relevant production of virulence factors, such as ß-hemolysin, lecithinase and cereulide, and its important resistance pattern to antimicrobial drugs. In conclusion, these new findings expand the understanding that this microorganism should not be neglected and new methods for tracking it should be considered.
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Bacillus cereus , Microbiología de Alimentos , Contaminación de Alimentos , Diálisis Renal , Factores de VirulenciaRESUMEN
Gold nanorods (GNRs) are increasingly being studied for diagnostic and therapeutic purposes. Green synthesis based methods with natural compounds as additives stand out as a hope in terms of better synthesis methodology, with advantages of producing potentially less toxic and, perhaps, biologically active GNRs due to influence of natural additives used during synthesis. Exploring green chemistry using different natural phenolic compounds, the present work reveals different in vitro activity of GNRs evaluated against different parasites that causes skin infectious diseases compared to GNRs produced by convencional seed mediated method. This approach brings advantages in producing active GNRs, with ease calling, less cytotoxic and with a better selectivity index (SI) than GNRs synthesized by conventional seed mediated synthesis, opening new possibilities for therapies. Natural compounds used in green syntheses were gallic acid (GA), resveratrol (RSV) and a purified fraction of the hydroalcoholic extract of Stryphnodendron obovatum. GNRs exhibited great activity against Leishmania braziliensis, and the dermatophytes Tricophyton rubrum, T. interdigitale and Microsporum gypseum. The anti-Leishmania and antidermatophytic activity of GNRs reinforce the applicability of GNRs in biomedical field and the influence of synthesis method in biological activity, showing benefits related to the seedless synthesis with natural compounds. In addition, these preliminary results indicate the possibility of exploring at maximum the physical and chemical properties of GNRs in addition to the biological activity itself, such as the development of topical antiparasitic formulations for association with phototherapy.
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Oro , Nanotubos , Oro/química , Resveratrol , Ácido Gálico/farmacología , AntiparasitariosRESUMEN
Lipophosphoglycan (LPG), the major Leishmania glycoconjugate, induces pro-inflammatory/immunosuppressive innate immune responses. Here, we evaluated functional/biochemical LPG properties from six Leishmania amazonensis strains from different hosts/clinical forms. LPGs from three strains (GV02, BA276, and LV79) had higher pro-inflammatory profiles for most of the mediators, including tumor necrosis factor alpha and interleukin 6. For this reason, glycoconjugates from all strains were biochemically characterized and had polymorphisms in their repeat units. They consisted of three types: type I, repeat units devoid of side chains; type II, containing galactosylated side chains; and type III, containing glucosylated side chains. No relationship was observed between LPG type and the pro-inflammatory properties. Finally, to evaluate the susceptibility against antileishmanial agents, two strains with high (GV02, BA276) and one with low (BA336) pro-inflammatory activity were selected for chemotherapeutic tests in THP-1 cells. All analyzed strains were susceptible to amphotericin B (AmB) but displayed various responses against miltefosine (MIL) and glucantime (GLU). The GV02 strain (canine visceral leishmaniasis) had the highest IC50 for MIL (3.34 µM), whereas diffuse leishmaniasis strains (BA276 and BA336) had a higher IC50 for GLU (6.87-12.19 mM). The highest IC50 against MIL shown by the GV02 strain has an impact on clinical management. Miltefosine is the only drug approved for dog treatment in Brazil. Further studies into drug susceptibility of L. amazonensis strains are warranted, especially in areas where dog infection by this species overlaps with those caused by Leishmania infantum.
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Anfotericina B , Leishmania , Anfotericina B/farmacología , Animales , Perros , Glicoesfingolípidos , Interleucina-6 , Leishmania/genética , Antimoniato de Meglumina/farmacología , Ratones , Ratones Endogámicos BALB C , Fosforilcolina/análogos & derivados , Factor de Necrosis Tumoral alfaRESUMEN
Background: Peripheral artery disease (PAD) has high prevalence and is associated with high risk of cardiovascular events. Surgical or endovascular intervention is necessary in chronic limb-threatening ischemia. Objectives: To evaluate the distribution of open and endovascular revascularizations in different regions of Brazil, analyzing the health system costs and mortality related to these procedures. Methods: A descriptive, cross-sectional, observational, epidemiological study was carried out to evaluate open and endovascular surgeries performed on the SUS public healthcare system in Brazil, from 2010 to 2020. Data were collected from the SUS Department of Informatics (Datasus). Results: Over the period analyzed, 83,218 admissions for open and endovascular surgeries were registered, with a total cost of R$ 333,989,523.17. There were more hospital admissions for percutaneous procedures (56,132) than for conventional surgery (27,086). Most of the procedures (83%) were performed in the country's Southeast and South regions, while the North region had the lowest number of procedures. Over the period evaluated, there was a decreasing trend for open procedures and an increasing trend for endovascular procedures. The average hospital stay was shorter for endovascular procedures (5.3 days) than for open surgery (10.2 days). The analysis of mortality related to these procedures revealed a higher rate of in-hospital mortality associated with open revascularization than with endovascular (5.24% vs. 1.56%). Conclusions: Endovascular techniques constituted the primary approach for revascularization treatment in critical limb-threatening ischemia, with a lower in-hospital mortality rate and shorter hospital stay when compared to open surgeries.
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Citrate functionalized iron oxide nanoparticles (IONPs) are employed for various purposes-including environmental remediation but the interaction of IONPs with aquatic contaminants is poorly understood. Among those, glyphosate-based herbicides are toxic and affect target organs such as the liver. Evaluations of livers of female Poecilia reticulata by exposures to IONPs at a concentration of 0.3 mg/L were performed with association to: (1) 0.65 mg of glyphosate per litter and (2) 1.3 mg of glyphosate per litter of Roundup Original, and (3) glyphosate P.A at 0.65 mg/L. These associations were carried out progressively, after 7, 14, and 21 days. We detected circulatory disturbances, inflammatory responses, activation of the immune system, regressive changes, and progressive responses with changes in the connective tissue and decreased glycogen reserve from days 14 to 21. Ultrastructural changes in the Disse space and microvilli of hepatocytes indicated decreased contact surface area. In general, the damage was time and concentration dependent, increasing from 7 to 14 days and tending to stabilize from 14 to 21 days. Therefore, herbicide-associated IONPs functioned as xenobiotics inducing intense cellular detoxification processes and activation of hepatic immune responses.
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Herbicidas , Poecilia , Animales , Femenino , Glicina/análogos & derivados , Herbicidas/toxicidad , Hígado , Nanopartículas Magnéticas de Óxido de Hierro , Poecilia/fisiología , GlifosatoAsunto(s)
Trasplante de Córnea , Úlcera de la Córnea , Infecciones Bacterianas del Ojo , Queratitis , Infecciones por Pseudomonas , Úlcera de la Córnea/tratamiento farmacológico , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Humanos , Lactante , Pseudomonas , Pseudomonas aeruginosaRESUMEN
Despite the increasing number of manuscripts describing potential alternative antileishmanial compounds, little is advancing on translating these knowledges to new products to treat leishmaniasis. This is in part due to the lack of standardisations during pre-clinical drug discovery stage and also depends on the alignment of goals among universities/research centers, government and pharmaceutical industry. Inspired or not by drug repurposing, metal-based antileishmanial drugs represent a class that deserves more attention on its use for leishmaniasis chemotherapy. Together with new chemical entities, progresses have been made on the knowledge of parasite-specific drug targets specially after using CRISPR/Cas system for functional studies. In this regard, Leishmania parasites undergoe post-translational modification as key regulators in several cellular processes, which represents an entire new field for drug target elucidation, once this is poorly explored. This perspective review describes the advances on antileishmanial metallodrugs and the elucidation of drug targets based on post-translational modifications, highlighting the limitations on the drug discovery/development process and suggesting standardisations focused on products addressed to who need it most.
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Antiprotozoarios , Leishmania , Leishmaniasis , Antiprotozoarios/química , Descubrimiento de Drogas , Humanos , Leishmaniasis/tratamiento farmacológico , Procesamiento Proteico-PostraduccionalRESUMEN
OBJECTIVE: Professionals working in intensive care units (ICUs) during the COVID-19 pandemic have been exposed to stressful situations and increased workload. The association between symptoms of traumatic stress disorders, substance abuse and personal/occupational characteristics of Brazilian COVID-19-ICU workers is still to be addressed. Our aim was to evaluate the prevalence of those conditions and to find if those associations exist. METHODS: In this observational, single-center, cross-sectional study, all professionals working in a COVID-19 ICU were invited to fill an anonymous form containing screening tools for traumatic stress disorders and substance abuse, and a section with questions regarding personal and occupational information. RESULTS: Three hundred seventy-six ICU professionals participated. Direct exposure to patients infected by COVID-19, history of relatives infected by COVID-19, and sex (female) were significantly associated with signs and symptoms of traumatic stress disorders. 76.5% of the participants had scores compatible with a diagnosis of traumatic stress disorders. Moreover, the prevalence of scores suggestive of Tobacco and Alcohol abuse were 11.7% and 24.7%, respectively. CONCLUSION: ICU workers had significantly elevated scores on both screening forms. Providing psycho-social support to ICU professionals may prevent future problems with traumatic stress disorders or substance abuse.