Periodontal evaluation after maxillary expansion with a tooth-bone-borne expander in growing patients : A randomized clinical trial.

PURPOSE: This two-arm parallel randomized controlled trial aimed to evaluate and compare periodontal changes due to rapid maxillary expansion (RME) using tooth-bone-borne and tooth-borne devices in growing patients via clinical examinations and cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Forty-two eligible patients (aged 11-14 years; transverse maxillary deficiency, posterior crossbite) were screened and divided into two groups based on the treatment received (randomization was performed using computer-generated numeric sequences): hybrid hyrax tooth-bone-borne group (TBB) and hyrax tooth-borne group (TB). The primary outcome was the change in cortical bone thickness (by CBCT). In addition, the clinical attachment level (CAL), gingival recession, and bleeding were assessed. Both examinations were performed before and 3 months after the activation phase. Intergroup comparisons were performed using analysis of covariance (ANCOVA; P < 0.05). RESULTS: Twenty-one patients (12 girls and 9 boys; mean initial age, 13.3 years) were included in the TBB group and 21 (5 girls and 16 boys; mean initial age, 13.2 years) were included in the TB group. The TB group exhibited a decrease in buccal bone thickness in the first premolars and first molars at all three evaluated levels. Specifically, tooth 14 at 3 mm from the enamel-cement junction showed a significant width reduction (0.7 mm; p < 0.001), accompanied by a notable increase in palatal cortical thickness at 6 mm of enamel-cement junction (1.13 mm; p < 0.001). CONCLUSIONS: RME resulted in buccal bone thickness reduction at the first premolar with hyrax treatment. In the molar region, both devices resulted in cortical bone alterations that were less pronounced in the TBB group.

Hybrid Nanosystem Formed by DOX-Loaded Liposomes and Extracellular Vesicles from MDA-MB-231 Is Effective against Breast Cancer Cells with Different Molecular Profiles.

Drug delivery selectivity is a challenge for cancer treatment. A hybrid pegylated pH-sensitive liposome-extracellular vesicle isolated from human breast cancer cell MDA-MB-231 was developed to investigate its in vitro activity against breast cancer cells of different molecular profiles to overcome this inconvenience. The hybrid nanosystem was produced by film hydration, and doxorubicin (DOX) was encapsulated in this system using the ammonium sulfate gradient method. The characterization of this hybrid nanosystem revealed a mean diameter of 140.20 ± 2.70 nm, a polydispersity index of 0.102 ± 0.033, an encapsulation efficiency of doxorubicin of 88.9% ± 2.4, and a great storage stability for 90 days at 4 °C. The fusion of extracellular vesicles with liposomes was confirmed by nanoflow cytometry using PE-conjugated human anti-CD63. This hybrid nanosystem demonstrated cytotoxicity against human breast cancer cell lines with different molecular subtypes, enhanced anti-migration properties, and exhibited similar cellular uptake to the free DOX treatment. Preliminary acute toxicity assessments using Balb/C female mice indicated a median lethal dose of 15-17.5 mg/kg, with no evidence of splenic, liver, heart, bone marrow, and renal damage at a dose of 15 mg/kg. These findings suggest the hybrid formulation as a versatile nanocarrier for the treatment of various breast cancer subtypes.

CLOCK gene circannual expression in cluster headache.

BACKGROUND: Cluster headache is a primary headache disorder characterized by bouts with circadian and circannual patterns. The CLOCK gene has a central role in regulating circadian rhythms. Here, we investigate the circannual CLOCK expression in a population of cluster headache patients in comparison to matched controls. METHODS: Patients with cluster headache were sampled two to four times over at least one year, both in or outside bouts, one week after each solstice and equinox. The expression of CLOCK was measured by quantitative real-time polymerase chain reaction (RT-PCR) in the peripheral blood. RESULTS: This study included 50 patients and 58 matched controls. Among the patient population, composed of 42/50 males (84%) with an average age of 44.6 years, 45/50 (90%) suffered from episodic cluster headache. Two to four samples were collected from each patient adding up to 161 samples, 36 (22.3%) of which were collected within a bout. CLOCK expression for cluster headache patients was considerably different from that of the control population in winter (p-value mean = 0.006283), spring (p-value mean = 0.000006) and summer (p-value mean = 0.000064), but not in autumn (p-value mean = 0.262272). For each season transition, the variations in CLOCK expression were more pronounced in the control group than in the cluster headache population. No statistically significant differences were found between bout and non-bout samples. No individual factors (age, sex, circadian chronotype, smoking and coffee habits or history of migraine) were related to CLOCK expression. CONCLUSIONS: We observed that CLOCK expression in cluster headache patients fluctuates less throughout the year than in the control population. Bout activity and lifestyle factors do not seem to influence CLOCK expression.

Occurrence of antibiotics, hormones and PFAs in surface water from a Nile tilapia aquaculture facility in a Brazilian hydroelectric reservoir.

This study assessed the occurrence of five antibiotics, three hormones, caffeine, and long and short-chain perfluoroalkyl and polyfluoroalkyl substances (PFASs) in surface water and feedstuff samples obtained from aquaculture cages in Três Marias reservoir in Brazil. This is the first work to evaluate the presence of PFAS in surface water used for aquaculture in Brazil. Solid-phase extraction and low temperature partitioning extraction followed by liquid chromatography coupled to mass spectrometry (LC-MS) were performed to process and analyze surface water samples and feedstuff, respectively. The ecotoxicological risk quotient was calculated for target compounds detected in water. Ciprofloxacin and caffeine were detected in all surface water samples. Pharmaceutical drugs ranged from 0.7 ng L-1 (trimethoprim) to 389.2 ng L -1 (ß-estradiol). Estrone (10.24 ng g-1) and ß-estradiol (66.20 ng g-1) were also found in feedstuff. Four PFASs (PFOA, PFDoA, PFTeDA, and PFBS) were detected (9.40-15.2 µg L-1) at levels higher than reported in studies conducted worldwide. Ecotoxicological risk assessment indicated high risks for caffeine and PFOA, PFDoA, and PFTeDA with RQ values from 10 to 103. These findings reveal risks to biodiversity, ecosystem integrity and human health considering possible intake of these contaminants by fish consumption due to potential bioaccumulation of these substances. Hence, it is critical to conduct more studies in this direction in Brazil and other low and middle-low-income countries.

The absence of eosinophils is associated with early metastatic lesions in Leishmania amazonensis-infected mice.

BACKGROUND: Eosinophils are granulocytes that rapidly increase frequency in the bloodstream during helminthic infections and allergic responses. They are found in tissue infected by Leishmania during early disease, but their role during infection is not entirely understood. OBJECTIVES: We aim to compare the disease due to Leishmania amazonensis in BALB/c and Δdbl-GATA1 mice, which lack eosinophils. METHODS: BALB/c and Δdbl-GATA1 mice infected with L. amazonensis were observed for several weeks. The parasite load and dissemination pattern were assessed. FINDINGS: The Δdbl-GATA1 mice developed an anticipated dissemination of L. amazonensis and a worsening disease. No differences were found in the lesion development or the parasite load in the footpad among Δdbl-GATA1 mice and BALB/c eight weeks after infection. However, nine weeks after infection, massive growth of metastatic lesions appeared in several parts of the skin in Δdbl-GATA1 mice, weeks earlier than BALB/c. We observed increased parasites in the bloodstream, probably an essential dissemination route. Thirteen weeks after infection, metastatic lesions were found in all Δdbl-GATA1 mice. MAIN CONCLUSION: These results suggest a protective role of eosinophils in delaying the disease caused by L. amazonensis, although several limitations of this mice strain must be considered.

Preclinical evaluation of L-fucoside from lapachol-loaded nanoemulsion as a strategy to breast cancer treatment.

Breast cancer prevails as the most common cancer in women, underscoring an urgent need for more effective therapies. This study explores the potential of our newly developed nanoemulsion containing a novel fucoside derivative of lapachol (NE-F-LapA) as an intravenous treatment strategy. We sought to overcome the solubility issues associated with fucoside with this improved drug delivery strategy that enhances tumor delivery and mitigates other dose-limiting toxicities. Nanoemulsion was prepared and characterized by DLS, zeta potential, encapsulation efficiency, and storage stability. Cytotoxicity against breast cancer cell lines (4T1 and MDA-MB-231) and non-tumor human fibroblasts (NTHF) were evaluated. In vivo assays included antitumoral activity performance and acute systemic toxicity in mice models. NE-F-LapA was synthesized and optimized to 200 nm size, - 20 mV zeta potential, and near-complete (>98%) drug encapsulation. Stability exceeded 6 months, and biological fluid exposure maintained suitable properties for administration. In vitro, NE-F-LapA showed high toxicity (3 µM) against 4T1 and MDA-MB-231, enhanced five times the breast cancer cell uptake and three times the selectivity when compared to normal cells. Systemic toxicity assessment in mice revealed no concerning hematological or biochemical changes. Finally, in a 4T1 breast tumor model, NE-F-LapA significantly inhibited growth by 50% of the subcutaneous 4T1 tumor and reduced lung metastases 5-fold versus control. Overall, tailored nanoemulsification of the lapachol derivative enabled effective intravenous administration and improved efficacy over the free drug, indicating promise for enhanced breast cancer therapy pending further optimization.

The absence of eosinophils is associated with early metastatic lesions in Leishmania amazonensis-infected mice

BACKGROUND Eosinophils are granulocytes that rapidly increase frequency in the bloodstream during helminthic infections and allergic responses. They are found in tissue infected by Leishmania during early disease, but their role during infection is not entirely understood. OBJECTIVES We aim to compare the disease due to Leishmania amazonensis in BALB/c and Δdbl-GATA1 mice, which lack eosinophils. METHODS BALB/c and Δdbl-GATA1 mice infected with L. amazonensis were observed for several weeks. The parasite load and dissemination pattern were assessed. FINDINGS The Δdbl-GATA1 mice developed an anticipated dissemination of L. amazonensis and a worsening disease. No differences were found in the lesion development or the parasite load in the footpad among Δdbl-GATA1 mice and BALB/c eight weeks after infection. However, nine weeks after infection, massive growth of metastatic lesions appeared in several parts of the skin in Δdbl-GATA1 mice, weeks earlier than BALB/c. We observed increased parasites in the bloodstream, probably an essential dissemination route. Thirteen weeks after infection, metastatic lesions were found in all Δdbl-GATA1 mice. MAIN CONCLUSION These results suggest a protective role of eosinophils in delaying the disease caused by L. amazonensis, although several limitations of this mice strain must be considered.

In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric ß-D-Glucopyranosyltriazole.

The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile.

Clinical acute presentation of lumbar facet joint ganglia with bilateral sciatica / Apresentação clínica aguda de quistos facetários lombares com ciatalgia bilateral / Presentación clinica aguda de quistes facetarios lumbares con dolor ciático bilateral

ABSTRACT Facet joint ganglia are benign cystic lesions located adjacent to a facet joint. The majority is asymptomatic. However, can cause important low-back pain and radiculopathy. Neurogenic deficit, claudication, and cauda equina syndrome have also been reported. The authors report two cases of acute low back pain with bilateral sciatica, dorsal foot dysesthesia, and hallux dorsiflexion/extension deficit, due to the presence of encapsulated cysts adjacent to the facet joints causing a significant reduction of the spinal canal. Urgent surgical decompression was performed in both patients with an uneventful recovery. Symptomatic facet joint ganglia is a highly unusual cause of back pain, although it can present with acute onset of bilateral sciatica and canal stenosis requiring urgent surgical decompression. This paper highlights facet joint synovial as a differential diagnosis of lumbar pain and describes two different surgical approaches with good outcomes. Level of Evidence IV; Case Series.

RESUMO: Os quistos facetários são lesões císticas benignas localizadas adjacentes a uma articulação facetária. A maioria é assintomática. No entanto, podem ser causa de importante dor lombar e radiculopatia. Estão ainda relatados casos de déficit neurogénico, claudicação e síndrome de cauda equina. Os autores apresentam dois casos de dor lombar aguda com ciatalgia bilateral, disestesia do dorso do pé e défice na dorsiflexão/extensão do hálux, causados por uma redução significativa do canal medular devido à presença de quistos encapsulados adjacentes às articulações facetarias. Os doentes foram submetidos a descompressão cirúrgica urgente com uma excelente recuperação. Os quistos facetários sintomáticas são uma causa rara de lombalgia, porém podem apresentar-se inicialmente com um quadro agudo de ciatalgia bilateral e estenose canalar com necessidade de descompressão cirúrgica urgente. Este artigo realça os quistos facetários como diagnóstico diferencial de lombalgia e descreve duas abordagens cirúrgicas diferentes com bons resultados. Nível de Evidência IV; Série de Casos.

RESUMEN: Los quistes facetarios son lesiones quísticas benignas situadas junto a una articulación facetaria. La mayoría es asintomática. Pero pueden causar dolor lumbar y radiculopatía importantes. También se han descrito déficit neurogénico, claudicación y síndrome de cauda equina. Los autores presentan dos casos de lumbalgia aguda con dolor ciático bilateral, disestesia del dorso del pie y déficit en la dorsiflexión/extensión del hallux, causados por una reducción significativa del canal medular debido a la presencia de quistes encapsulados adyacentes a las articulaciones facetarias. Los pacientes fueron sometidos a descompresión quirúrgica urgente con una excelente recuperación. Los quistes facetarios sintomáticos son una causa poco frecuente de lumbalgia, aunque pueden presentarse inicialmente con un cuadro agudo de dolor ciático bilateral y estenosis del canal que requiere descompresión quirúrgica urgente. Este artículo destaca los quistes facetarios como diagnóstico diferencial de la lumbalgia y describe dos abordajes quirúrgicos diferentes con buenos resultados. Nivel de Evidencia IV; Serie de Casos.

Tomographic score (RAD-Covid Score) to assess the clinical severity of the novel coronavirus infection

ABSTRACT Objectives: The severity of pulmonary Covid-19 infection can be assessed by the pattern and extent of parenchymal involvement observed in computed tomography (CT), and it is important to standardize the analysis through objective, practical, and reproducible systems. We propose a method for stratifying the radiological severity of pulmonary disease, the Radiological Severity Score (RAD-Covid Score), in Covid-19 patients by quantifying infiltrate in chest CT, including assessment of its accuracy in predicting disease severity. Methods: This retrospective, single-center study analyzed patients with a confirmed diagnosis of Covid-19 infection by real-time reverse-transcriptase polymerase chain reaction, who underwent chest CT at hospital admission between March 6 and April 6, 2020. CT scans were classified as positive, negative, or equivocal, and a radiological severity score (RAD-Covid Score) was assigned. Clinical severity was also assessed upon hospital admission. Results: 658 patients were included. Agreement beyond chance (kappa statistic) for the RAD-Covid Score was almost perfect among observers (0.833), with an overall agreement of 89.5%. The RAD-Covid Score was positively correlated with clinical severity and death, i.e., the higher the RAD-Covid Score, the greater the clinical severity and mortality. This association proved independent of age and comorbidities. Accuracy of this score was 66.9%. Conclusions: The RAD-Covid Score showed good accuracy in predicting clinical severity at hospital admission and mortality in patients with confirmed Covid-19 infection and was an independent predictor of severity.

Perfil do gestor e práticas de gestão municipal no Sistema Único de Saúde (SUS) de acordo com porte populacional nos municípios do estado do Rio Grande do Sul / Manager profile and practices of county health management in the Unified Health System (SUS) according to population size in the municipalities of the Rio Grande do Sul state

Resumo O estudo buscou conhecer quem são os gestores municipais de saúde e práticas realizadas no âmbito de gestão. Possuiu delineamento transversal. A metodologia contou com o envio de um questionário eletrônico às secretarias de saúde dos 497 municípios do estado do Rio Grande do Sul (RS). Destes, 297 retornaram (59,75%). Contudo, foram considerados na análise estatística apenas os questionários com mais de 50% de respostas válidas (n = 264). A análise contou com o cálculo da distribuição das variáveis e com testes de qui-quadrado, onde o porte populacional foi considerado variável independente. A maioria foi composta por mulheres, com escolaridade alta e distintas formações, média de idade de 43,76 anos, cor branca. A média de gastos com saúde foi de ≈20% das receitas. Houve consenso quanto na insuficiência dos recursos. Quanto ao porte populacional, 79,92% possuíam ≤ 20.000 habitantes. Diferenças significativas foram observadas na gestão de municípios de distintos portes, tanto nas prioridades, quanto nas dificuldades. O estudo permitiu conhecer parcialmente a realidade da gestão municipal. Além disso, os resultados sugeriram a necessidade de novas pesquisas sobre a feminilização da gestão, avaliação de processos de trabalho e impactos da política de austeridade.

Abstract This study intended to gather who are the county health managers and the practices performed in management. It is based on a cross-sectional design. The methodology involved the use of electronic questionnaire, which was sent to the health departments of the 497 municipalities of the state of Rio Grande do Sul (RS). Of these, 297 were answered (59.75%). However, only those with more than 50% of valid answers (n = 264) were included in the statistical analysis. The analysis included the calculation of the distribution of variables and chi-square testes, taking population size as an independent variable. Most managers were women; graduated; from different professional backgrounds; average age of 43.76 years-old, and white. The average health expenditure in the municipalities was ≈ 20% of revenues. There was a consensus on the insufficiency of resources. With regards to population size, 79.92% presented with ≤ 20,000 inhabitants. Statistically significant differences were found in the management of municipalities of different sizes, both in terms of priorities and difficulties. The study allowed to partially understanding the reality of municipal management. These results indicate the need to further investigate the feminization of health management, working process assessment, and the impacts of economical austerity policy.

Classificação WifI: o novo sistema de classificação da Society for Vascular Surgery para membros inferiores ameaçados, uma revisão de literatura / WIfI classification: the Society for Vascular Surgery lower extremity threatened limb classification system, a literature review

Resumo A Society for Vascular Surgery propôs nova classificação para o membro inferior ameaçado, baseada nos três principais fatores influenciadores do risco de amputação do membro: ferida (Wound, W), isquemia (Ischemia, I) e infecção do pé (foot Infection, fI): a classificação WIfI. Esta abrange também os diabéticos, anteriormente excluídos do conceito de isquemia crítica do membro devido a seu quadro clínico complexo. O objetivo da classificação era fornecer estratificação de risco precisa e precoce ao paciente com membro inferior ameaçado; auxiliar no manejo clínico, permitindo comparar terapias alternativas; e predizer o risco de amputação em 1 ano e a necessidade de revascularização. O objetivo deste estudo é reunir os principais pontos abordados sobre a classificação WIfI no meio científico. A maior parte dos estudos de validação da classificação demonstram sua associação à predição de salvamento do membro, eventos de reintervenção, amputação e estenose, taxas de amputação maior e menor, sobrevida livre de amputação, e cicatrização de feridas.

Abstract The Society for Vascular Surgery has proposed a new classification system for the threatened lower limb, based on the three main factors that have an impact on limb amputation risk: Wound (W), Ischemia (I) and foot Infection ("fI") - the WIfI classification. The system also covers diabetic patients, previously excluded from the concept of critical limb ischemia because of their complex clinical condition. The classification's purpose is to provide accurate and early risk stratification for patients with threatened lower limbs; assisting with clinical management, enabling comparison of alternative therapies; and predicting risk of amputation at 1 year and the need for limb revascularization. The objective of this study is to collect together the main points about the WIfI classification that have been discussed in the scientific literature. Most of the studies conducted for validation of this classification system prove its association with factors related to limb salvage, such as amputation rates, amputation-free survival, prediction of reintervention, amputation, and stenosis (RAS) events, and wound healing.

Radiolabeling of cidofovir with technetium-99m and biodistribution studies

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.

Tarsal Navicular Fracture in a Parkour Practitioner, a Rare Injury - Case Report and Literature Review / Fratura do escafoide társico em um praticante de parkour, uma lesão rara - Relato de Caso e Revisão da Literatura

Abstract Tarsal navicular fractures, as well as other midfoot injuries, are rare, and can result in severe impairment if not properly treated. Parkour, a modern sport, is gaining popularity among young individuals in urban areas, and is prone to result in high-energy trauma, which is scarcely described in the literature. The following is a report of a rare case of tarsal navicular fracture in a 17-year-old male, sustained during parkour practice, which was treated successfully with open reduction and internal fixation. The description of the case emphasizes the challenges of its approach; the discussion highlights the treatment options and goals. The case should also raise awareness about the increasing occurrence of these uncommon lesions.

Resumo As fraturas do escafoide társico, bem como outras lesões do médiopé, são raras e podem resultar em incapacidade grave se não forem tratadas adequadamente. Parkour, um esporte moderno, está ganhando popularidade entre os jovens em áreas urbanas, e é propenso a traumatismos de alta energia, sendo estes escassamente descritos na literatura. O presente relato trata de um caso de fratura rara do escafoide társico em um paciente do sexo masculino de 17 anos, ocorrida durante a prática de parkour, que foi tratada com sucesso, com redução aberta e fixação interna. A descrição do caso enfatiza os desafios na sua abordagem; a discussão destaca as opções de tratamento e seus objetivos. O caso também deve alertar sobre a ocorrência crescente dessas lesões incomuns.

Colonoscopia com infusão de água: revisão sistemática / Water infusion colonoscopy: a systematic review

Objetivo: verificar os benefícios do método de colonoscopia com água versus ar, e esclarecer as limitações dos estudos e revisões sistemáticas preexistentes em relação à taxa e tempo de intubação cecal, taxa de detecção de adenomas, duração da colonoscopia, e incidência de dor. Método: revisão sistemática da literatura sem metanálise. Resultados: em relação à taxa de intubação cecal, não houve aumento significante com o método de água; o tempo de intubação cecal foi significantemente mais longo com o método de água em dois estudos; a taxa de detecção de adenomas apresentou-se numericamente maior, sem apresentar diferença significante; a duração total do exame foi significantemente maior no método de água em apenas um estudo; em relação à dor, houve redução significativa da dor no método com água em relação ao método com insuflação de ar. Conclusão: o principal benefício do método de colonoscopia com infusão de água é a redução significativa da dor durante o procedimento, entretanto, foram encontrados diversos problemas em relação aos dez estudos avaliados e às revisões sistemáticas preexistentes. Concluiu-se pela necessidade de maiores pesquisas para confirmação dos dados.

Objective: to check the benefits of water colonoscopy method versus air insuflation colonoscopy method, and clarify the limitations of the pre-existing studies and systematic reviews in relation to the cecal intubation rate and time, adenoma detection rate, procedural time, and pain incidence. Method: systematic literature review without meta-analysis. Results: regarding the cecal intubation rate, the water method does not show significant increase; cecal intubation time was significantly longer with the water method, in two studies; the adenomas detection rate had presented numerically greater, although there was no significant difference; total colonoscopy procedural time was significantly greater in water method, only in one study; in relation to pain, there was a statistically significant reduction in pain with water method, compared to the air insufflation method. Conclusion: the main benefit of the water colonoscopy method is significant reduction in pain during the procedure. However, several problems were found in the ten assessed studies and in pre-existing systematic reviews. We concluded by the need for further research to confirm the data.

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

Background Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol.L−1 (S. aureus) and 10.10 μmol.L−1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.(AU)

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m

Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 mol.L1 (S. aureus) and 10.10 mol.L1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 g of LyeTx I-K-HYNIC; 250 g of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

Resistência a metais pesados, antimicrobianos e formação de biofilme em cepas de Escherichia coli isoladas em praias de São Luís - Maranhão / Resistance to heavy metals, antimicrobial and biofilm formation in Escherichia coli isolated from beaches of São Luis, Maranhão, Brazil

A cidade de São Luís, capital do estado do Maranhão, possui um sistema ineficiente de tratamento de seus efluentes e boa parte deles é lançada nos rios ou diretamente nas praias. Este trabalho teve como objetivo avaliar o grau de resistência aos metais pesados de 39 cepas de E.coli, isoladas da água de praias da cidade, além de sua suscetibilidade a antibióticos e sua capacidade de produzir biofilme. A análise da resistência aos metais pesados foi realizada pelo método de diluições sucessivas nas concentrações de 1 a 16mM.O teste de sensibilidade, ou antibiograma, foi executado pelo método de difusão em disco, utilizando-se os seguintes antibióticos: Aztreonam, Imipenem, Cefalotina, Ampicilina/Sulbactam, Gentamicina, Ampicilina, Cefuroxima sódica, Amoxicilina, Piperacilina+Tazobactam (TZP), Trimetoprim-Sulfametoxazol (SXT) e Amoxicilina+Ácido Clavulânico (AMC). Para detecção de biofilme nas cepas de E. coli, foram utilizadas as técnicas de Ágar Vermelho Congo (AVC) e Espectrofotometria (ESP). Os resultados mostraram 2 cepas tolerantes a concentrações de Hg a 1mM, 9 cepas resistentes ao Cu e Cd a 4mM e 12 ao Ni a 4mM. O exame de susceptibilidade aos antibióticos mostrou os seguintes percentuais de resistência das amostras: 15 por cento a ATM, 95 por cento a KF, 85 por cento a ASB, 85 por cento a CN, 87 por cento a AMP, 13 por cento a CXM, 5 por cento a TZP, 74 por cento a SXT e 18 por cento a AMC. Quanto à produção de biofilme, 20 por cento apresentaram elevada produção, 36 por cento fraca produção e 44 por cento não produziram. Pela técnica de espectrofotometria, somente 1 cepa (2,5 por cento) revelou-se produtora moderada de biofilme, 5 (12,5 por cento) foram classificadas como não produtoras e as demais, 34 (85 por cento), como fracas produtoras. A presença de bactérias com múltiplos perfis de resistência nas praias de São Luís pode representar riscos para a saúde pública e causar alterações diretas na ecologia das comunidades de micro-organismos marinhos.

The city of São Luís, located in the State of Maranhão has inefficient treatment of sewage, which isreleased into the rivers or directly on the beaches. This study evaluated the resistance of 39 strainsof Escherichia coli to Cu, Ni, Cd and Hg, their susceptibility to antibiotics and ability for biofilmproduction. Samples were collected from the beaches of Ponta D’Areia, São Marcos, Calhau andOlho d’Água. The antibiotic susceptibility tests were performed by the disk diffusion method withthe following antibiotics: Aztreonam (ATM), Imipenem (IMP), Cephalothin (KF), Ampicillin /Sulbactam (ASB), Gentamicin (CN), Ampicillin (AMP), Cefuroxime sodium (CXM), Amoxicillin(AML), Piperacillin Tazobactam (TZP), Trimethoprim-sulfamethoxazole (SXT) and Amoxicillin+ clavulanic acid (AMC). The detection of biofilm production was performed using Congo RedAgar (CRA) and spectrophotometry (ESP). The results showed 2 strains were Hg tolerant (1mM), 9 strains resistant to Cu and Cd (4 mM) and 12 strains resistant to Ni (4 mM). The antibioticsusceptibility tests showed resistance to ATM (15 percent of samples), KF (95 percent), BSA (85 percent), CN (5 percent),AMP (87 percent), CXM (13 percent), TZP (5 percent), SXT (74 percent) and AMC (18 percent). For the synthesis of biofilm inCRA 20 percent showed strong production, 36 percent low and 44 percent did not produce. By spectrophotometryonly 1 (2.5 percent) proved to be a moderate biofilm producer, 5 (12.5 percent) were classified as non-producersand the other 34 (85 percent) weak producers. The presence of bacteria with antimicrobial and heavy metalresistance profiles, and production of biofilms represents a public health risk and cause of directchanges in ecological communities of marine microorganisms.

Use of intravitreal bevacizumab or triamcinolone acetonide as a preoperative adjunct to vitrectomy for vitreous haemorrhage in diabetics / Injeção intravítrea de bevacizumabe ou triancinolona como adjuvantes da vitrectomia posterior no tratamento da hemorragia vítrea em diabéticos

PURPOSE: To evaluate the effect of preoperative intravitreal bevacizumab (IVB) or triamcinolone (IVT) on the rate of early postvitrectomy hemorrhage in proliferative diabetic retinopathy (PDR). METHODS: Eligible eyes were assigned randomly to 1 of 3 groups: the IVB group received 1.25 mg bevacizumab, the IVT group received 4,0mg triamcinolone and the control group underwent a sham procedure. The primary outcome measure was the incidence of early postvitrectomy hemorrhage. Secondary outcome measures included changes in visual acuity (BCVA) and adverse events. RESULTS: Twenty and seven eyes, 9 in each group were randomized. The incidence of vitreous hemorrhage was lower in the IVB group (p=0.18). Postoperative vitreous hemorrhage at 1 month also was less in the IVB group compared with the control group (p > 0.05). The rate of bleeding immediately after surgery was higher in IVT group with 4 (44.4%) cases. The overall mean visual acuity was 1.72 ± 0.37 logMAR preoperatively and 1.32 ± 0.73 logMAR in 6 months after surgery. Accessing visual acuity by group evidenced that the IVB group had initial mean logMAR VA of 1.87 and 1.57 logMAR VA at the six months (p = 0.84). In IVT group, initial mean VA was 1.75 logMAR and 0.96 logMAR VA at six months (p < 0.001). And in control group, the initial mean VA was 1.85 logMAR and 1.57 logMAR VA at six months (p= 0.34). CONCLUSION: Intravitreal injection of bevacizumab 1 week before vitrectomy seems to reduce the incidence of early postvitrectomy hemorrhage in diabetic patients. There was a better visual acuity outcome in the triamcinolone group.

OBJETIVO: Avaliar o efeito no pré-operatório da injecao intravítrea de bevacizumab (IVB) ou triancinolona (IVT) sobre a taxa de hemorragia precoce pos-vitrectomia na retinopatia diabética proliferativa. MÉTODOS: Os olhos foram distribuídos em três grupos: IVB - 1,25 mg bevacizumab, IVT - 4,0 mg de triancinolona e o grupo controle - simulação da injeção. O objetivo primário foi a avaliação da incidência da hemorragia precoce pós-vitrectomia. Os objetivos secundários incluíram mudanças na acuidade visual corrigida e eventos adversos relacionados à injeção. RESULTADOS: Dos Vinte e sete olhos, 9 foram randomizados em cada grupo. A incidência de hemorragia vítrea foi menor no grupo IVB (P=0,18). A hemorragia vítrea em 1 mês também foi menor no grupo IVB (P > 0,05). A taxa de sangramento pós-operatório imediato foi maior no grupo IVT com 4 (44,4%) dos casos. A média da acuidade visual (AV) foi de 1,72 ± 0,37 logMAR no pré-operatório e 1,32 ± 0,73 logMAR em 6 meses após a cirurgia. Analisando a AV por grupo evidenciamos que o grupo IVB tinha inicialmente AV média logMAR de 1,87 e AV logMAR de 1,57 em seis meses (p = 0,84). No grupo IVT, a média inicial de AV foi de 1,75 logMAR e 0,96 logMAR em seis meses (p < 0,001). E no grupo controle, a média inicial foi de 1,85 logMAR e 1,57 logMAR no seis meses (p = 0,34). CONCLUSÃO: A injeção intravítrea de bevacizumab antes da vitrectomia parece diminuir a incidência de hemorragia vítrea precoce pós-vitrectomia em diabéticos. Houve um melhor resultado na acuidade visual no grupo da triancinolona.

Detecção de enteropatógenos e teste de susceptibilidade a agentes sanitizantes de cepas diarreiogênicas de Escherichia coli isoladas das praias de São Luís - Maranhão / Enteropathogens detection and susceptibility testing to sanitizer agents of diarrheagenic Escherichia coli strains isolated from the beaches of São Luís, Maranhão, Brazil

Na cidade de São Luís, capital do estado do Maranhão, é ineficaz o tratamento de efluentes, os quais são lançados in natura nos recursos hídricos. Isso evidencia que, no ambiente costeiro,podem existir indicadores de contaminação fecal. Amostras das praias Ponta dAreia, São Marcos,Calhau e Olho dÁgua foram analisadas com o objetivo de detectar os enteropatógenos e as linhagens diarreiogênicas de Escherichia coli ali presentes e, além disso, testar a susceptibilidade a agentes sanitizantes das linhagens de E. coli diarreiogênicas. Em todos os pontos de coleta foramidentificadas espécies de E. coli, Serratia liquefaciens, Hafnia alvei, Salmonella spp., Serratia sp. Ascepas de E. coli diarreiogênicas, identificadas pela Reação em Cadeia de Polimerase (PCR), ficaram assim distribuídas: 82por cento de E. coli enterotoxigênica (ETEC), 9por cento de E. coli enterohemorrágica (EHEC) e 9por cento de E. coli enteroagregativa (EAEC). Os agentes sanitizantes testados foram: detergente, álcool doméstico e hipoclorito de sódio. Este último apresentou maior ação bactericida sobre todas as linhagens de E. coli. O estudo mostrou que os problemas de saneamento local têmcontribuído para a contaminação das praias de São Luís por microrganismos resistentes a agentes sanitizantes e que representam riscos à saúde pública.