Effects of a high-fat diet on the bone structure of Wistar rats: a systematic review.

CONTEXT: Saturated fats found in diets known as high-fat, cafeteria, or Western diets appear to have a negative effect on bone structure; however, few studies have focused on investigating this association, and the data available in the literature remain controversial. OBJECTIVE: The aim of the current review was to investigate the effects of a high-fat dietary intake on the bone structure of Wistar rats. DATA SOURCES: A search for articles was carried out in the Pubmed/MEDLINE, Web of Science, Embase, and Scopus databases. DATA EXTRACTION: In total, 447 articles were found in the initial search; 5 articles were included in the systematic review, after application of the exclusion criteria. DATA ANALYSIS: The review was guided by the PICOS strategy and based on the PRISMA protocol for animal reviews. CONCLUSION: High-fat diets appear to affect bone structure of Wistar rats. Diet composition and exposure time are the factors determining the strength of the effect.

CLEC5A expression can be triggered by spike glycoprotein and may be a potential target for COVID-19 therapy.

The immune response is crucial for coronavirus disease 19 (COVID-19) progression, with the participation of proinflammatory cells and cytokines, inducing lung injury and loss of respiratory function. CLEC5A expression on monocytes can be triggered by viral and bacterial infections, leading to poor outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to induce neutrophil activation by CLEC5A and Toll-like receptor 2, leading to an aggressive inflammatory cascade, but little is known about the molecular interactions between CLEC5A and SARS-CoV-2 proteins. Here, we aimed to explore how CLEC5A expression could be affected by SARS-CoV-2 infection using immunological tools with in vitro, in vivo, and in silico assays. The findings revealed that high levels of CLEC5A expression were found in monocytes from severe COVID-19 patients in comparison with mild COVID-19 and unexposed subjects, but not in vaccinated subjects who developed mild COVID-19. In hamsters, we detected CLEC5A gene expression during 3-15 days of Omicron strain viral challenge. Our results also showed that CLEC5A can interact with SARS-CoV-2, promoting inflammatory cytokine production, probably through an interaction with the receptor-binding domain in the N-acetylglucosamine binding site (NAG-601). The high expression of CLEC5A and high levels of proinflammatory cytokine production were reduced in vitro by a human CLEC5A monoclonal antibody. Finally, CLEC5A was triggered by spike glycoprotein, suggesting its involvement in COVID-19 progression; therapy with a monoclonal antibody could be a good strategy for COVID-19 treatment, but vaccines are still the best option to avoid hospitalization/deaths.

Does fructose have a protective role on migraine?-experimental evidence in a rat model of metabolic syndrome under omega-3 supplementation.

Background: Migraine is a highly disabling disease, for which current therapies are limited to symptom alleviation. There is compelling evidence linking migraine with metabolic disorders, but the causal relationship is not clear. Omega-3 (n-3) fatty acids have anti-inflammatory properties, with clear benefits in metabolic disorders, but its effects on migraine remains to be tested. We hypothesized that fructose-induced metabolic syndrome could aggravate migraine by increasing neuroinflammation and that n-3 treatment could mitigate it. Methods: Male Wistar rats were used. Animals that received 10% high fructose diet (HFD) or tap water were subdivided into two additional groups: with or without n-3 supplementation. Fifteen days before euthanasia, each group was subdivided into two additional groups: with or without nitroglycerin (NTG)-induced migraine. Results: HFD lessened the migraine-like painful symptoms, as indicated by decreased grimace scores, which paralleled with reduced CGRP and leptin serum levels, increased hypothalamic CGRP, and decreased hypothalamic adiponectin and IL-6. There was a recovery of body and adipose tissue weight, besides a reduction of crown-like structures (CLS) in the inguinal adipose tissue. N-3 supplementation had no effect on NTG-related pain, but it decreased body and adipose tissue weight of HFD and tap water NTG-injected rats. N-3 improved NTG-related affective behavior and inflammatory parameters in tap water NTG-injected rats, with decreased hypothalamic TNF, serum CGRP and inguinal adipose-tissue CLS. Conclusions: HFD relieved NTG-induced pain, possibly due to decreased energy expenditure, minimizing migraine energy needs. N-3 exhibited favorable effects regarding affective behavior and central and peripheral inflammation, irrespective of HFD.

Chronic Pain in the Elderly: Mechanisms and Perspectives.

Chronic pain affects a large part of the population causing functional disability, being often associated with coexisting psychological disorders, such as depression and anxiety, besides cognitive deficits, and sleep disturbance. The world elderly population has been growing over the last decades and the negative consequences of chronic pain for these individuals represent a current clinical challenge. The main painful complaints in the elderly are related to neurodegenerative and musculoskeletal conditions, peripheral vascular diseases, arthritis, and osteoarthritis, contributing toward poorly life quality, social isolation, impaired physical activity, and dependence to carry out daily activities. Organ dysfunction and other existing diseases can significantly affect the perception and responses to chronic pain in this group. It has been proposed that elderly people have an altered pain experience, with changes in pain processing mechanisms, which might be associated with the degeneration of circuits that modulate the descending inhibitory pathways of pain. Aging has also been linked to an increase in the pain threshold, a decline of painful sensations, and a decrease in pain tolerance. Still, elderly patients with chronic pain show an increased risk for dementia and cognitive impairment. The present review article is aimed to provide the state-of-art of pre-clinical and clinical research about chronic pain in elderly, emphasizing the altered mechanisms, comorbidities, challenges, and potential therapeutic alternatives.

Imaging the External Ear: Practical Approach to Normal and Pathologic Conditions.

The external ear (EE) is an osseous-cartilaginous structure that extends from the auricle to the tympanic membrane. It is divided into two parts: the auricle (or pinna) and the external auditory canal (EAC). Given the ease of access to the EE, imaging studies are not always needed to make a diagnosis. However, when lesions block visual access to areas deep to the EE abnormality, complications are suspected, or there is lack of response to treatment, imaging becomes essential. A basic understanding of the embryologic development and knowledge of the anatomy of the auricle and EAC are useful for accurate diagnosis of EE lesions. Congenital, traumatic, inflammatory, neoplastic, and vascular conditions can affect the EE. An overview of the anatomy and embryologic development of the EE is presented, with discussion and illustrations of common and uncommon conditions that affect EE structures and a focus on the CT and MRI features that are of interest to radiologists. CT is usually the first diagnostic modality used to evaluate the EAC and is the superior method for demonstrating bone changes. MRI provides excellent tissue characterization and enables one to better define lesion extension and perineural tumor spread. In addition, a flowchart to facilitate the differential diagnosis of EE abnormalities is provided. Online supplemental material is available for this article. ©RSNA, 2022.

Central and peripheral effects of environmental enrichment in a mouse model of arthritis.

This study analyzed whether environmental enrichment (EE) modulates the nociceptive and inflammatory responses in the mouse model of arthritis induced by Complete Freund's Adjuvant (CFA). Ninety male mice (C57BL/6-JUnib, 4-weeks-old; 20-25 g) were distributed into EE and standard (SE) groups. For EE, mice were kept in bigger cages using an alternation of materials to chew (wood and paper), for nesting (cotton), to use as hiding places (plastic tunnels), and for voluntary exercise (wheel running). Arthritis was induced by an injection of CFA (50 µL) into the right hind paw or saline solution in the control group. Separate groups received the anti-inflammatory drug dexamethasone (0.5 mg/kg; every 48 h). Inflammatory and pain measurements were performed from 1 to 35 days after CFA administration. EE per se reduced the acute paw edema formation and arthritis scores. The serum levels of tumor necrosis factor (TNF) were undetectable in any experimental groups. EE diminished the immunopositivity for the microglia marker IBA1 in the pre-frontal cortex, with slight changes for hippocampal GFAP-positive activated astrocytes. Finally, EE induced a marked increment of brain-derived nerve factor (BDNF) expression in the hippocampus, an effect that was fully prevented by dexamethasone. These data bring novel evidence on the peripheral and central effects of EE in a mouse arthritis model.

Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice.

Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals. Physiological (ITT) and molecular analysis (immunoblotting, and RT-qPCR) were performed. The contents of RhoA and ROCK2 protein were decreased in skeletal muscle of obese mice compared to control mice but were restored to normal levels in response to physical exercise. The exercised animals also showed higher phosphorylation of insulin receptor substrate 1 (IRS1 Serine 632/635) and protein kinase B (Akt) in the skeletal muscle. However, phosphatase and tensin homolog (PTEN) and protein-tyrosine phosphatase-1B (PTP-1B), both inhibitory regulators for insulin action, were increased in obesity but decreased after exercise. The impact of ROCK2 action on muscle insulin signaling is further underscored by the fact that impaired IRS1 and Akt phosphorylation caused by palmitate in C2C12 myotubes was entirely restored by ROCK2 overexpression. These results suggest that the exercise-induced upregulation of RhoA-ROCK2 signaling in skeletal muscle is associated with increased systemic insulin sensitivity in obese mice and further implicate that muscle ROCK2 could be a potential target for treating obesity-linked metabolic disorders.

Psychological symptoms and salivary inflammatory biomarkers in patients with dentofacial deformities: a case-control study.

Individuals with dentofacial deformities often display a low quality of life (QoL) through biological mechanisms that remain unraveled. In this case-control study, the salivary levels of cytokines, glutamate, and kynurenine metabolites were assessed in patients undergoing orthognathic surgery (OS), while correlating these parameters with QoL and psychological symptoms. Thirty-six patients were enrolled in control (under orthodontic treatment) and test (undergoing OS) groups, matched by age and sex. The QoL was assessed through the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Orthognathic Quality of Life Questionnaire (OQLQ). The psychological symptoms were evaluated by the Satisfaction with Life Scale, the Rosenberg Self-Esteem Scale (RSES), and the Depression, Anxiety, and Stress Scale-21 (DASS-21). The salivary levels of IL-1ß, IL-6, IL-10, glutamate, and kynurenine metabolites were evaluated. The OQLQ demonstrated increased QoL scores in the test group, regarding social aspects, facial esthetics, and function domains, without significant differences in respect to the other surveys. These patients displayed higher IL-1ß and glutamate levels; conversely, the kynurenine metabolites were unaltered. The glutamate levels positively correlated with the OQLQ function scores. The data brings novel evidence about the psychobiological features of patients with dentofacial deformities, showing salivary variations of inflammatory biomarkers in these individuals.

Individual effect of shear rate and oxygen transfer on clavulanic acid production by Streptomyces clavuligerus.

The production of biocompounds through the cultivation of filamentous microorganisms is mainly affected by Oxygen Transfer Rate (OTR) and shear rate ([Formula: see text]) conditions. Despite efforts have been made to evaluate the effect of operating variables (impeller speed, N; and airflow rate, ϕair) on clavulanic acid production, no analysis regarding the effect of OTR and [Formula: see text] was made. Then, the aim of this study was to evaluate the dissociated effect of physical phenomena such as oxygen transfer and shear rate in the production of clavulanic acid from Streptomyces clavuligerus using a stirred tank bioreactor. Streptomyces clavuligerus cultivations were performed at five different OTR and [Formula: see text] conditions by manipulating the operating conditions (N, ϕair, and gas inlet composition). Cultivations performed at equal impeller speed (600 rpm, similar [Formula: see text]) using oxygen enrichment, showed that CA productivity (ProdCA) was positively affected by OTR increase. Subsequently, the different shear conditions (achieved by varying the impeller speed) lead to an increase in CA production levels. Despite both OTR and shear rate positively enhanced CA productivity, [Formula: see text] exhibited the highest impact: an increase of 145% in OTRinitial enhanced the clavulanic acid productivity of about 29%, while an increment in the shear rate of 134% raised the ProdCA in 53%.

Response of lactating dairy cows fed different supplemental zinc sources with and without evaporative cooling to intramammary lipopolysaccharide infusion: metabolite and mineral profiles in blood and milk.

The objective of this study was to determine the effect of evaporative cooling and dietary supplemental Zn source on blood metabolites, insulin and mineral concentrations, and milk mineral concentrations following intramammary lipopolysaccharide (LPS) infusion. Seventy-two multiparous Holstein cows were assigned to one of four treatments with a 2 × 2 factorial arrangement. Treatments included two environments: with or without evaporative cooling using fans and misters over the freestall and feedbunk, and two dietary sources of supplemental Zn: 75 mg/kg of dry matter (DM) supplied by Zn hydroxychloride (inorganic Zn; IOZ) or Zn hydroxychloride (35 mg of Zn/kg of DM) + Zn-Met complex (ZMC; 40 mg of Zn/kg of DM). A subset of cows (n = 16; 263 ± 63 d in milk) was infused with 10 µg of LPS or a saline control in the left or right rear quarters on day 34 of the environmental treatment. Individual milk samples collected from LPS-infused quarters at -4, 0, 6, 12, 24, 48, 72, 96, and 144 h relative to infusion were analyzed for minerals. Blood samples were collected at the same time with an additional sample collected at 3 h post-infusion to analyze glucose, nonesterified fatty acids (NEFA), insulin, and minerals. Cooling by time interactions (P ≤ 0.07) were observed for plasma glucose, NEFA, and serum insulin. Compared with cooled cows, non-cooled cows had lower concentrations of plasma glucose except at 3 h following intramammary LPS infusion, greater serum insulin at 3 and 12 h, and lower plasma NEFA at 24 and 48 h after infusion. Relative to cooled cows, non-cooled cows tended (P = 0.07) to have lower serum K concentration and had lower (P < 0.01) serum Zn 6 h following infusion (cooling by time interaction: P < 0.01). Relative to ZMC cows, IOZ cows had greater (P ≤ 0.09) concentrations of plasma Se, skim milk Na and Se, and skim milk Na to K ratio. Regardless of treatment, intramammary LPS infusion reduced (P < 0.01) serum or plasma concentrations of Ca, Mg, Zn, Fe, and Se, but increased (P < 0.01) their concentration in skim milk. In conclusion, deprivation of cooling resulted in more rapid and prolonged insulin release and influenced the systemic and mammary mineral metabolism during mammary inflammation induced by LPS of lactating dairy cows. Dietary supplementation of Zn-Met complex reduced blood and milk Se concentrations compared with cows fed Zn from an inorganic source.

Structural and functional impacts of E5 genetic variants of human papillomavirus type 31.

Persistent infections caused by high-risk human papillomavirus (HR-HPV) are important, for the development of cervical lesions, but environmental and genetic factors are also related in the process of carcinogenesis. Among the genetic factors, the genetic variants of HR-HPV appear to be related to the risk of persistent infections. Therefore, the present study investigates variants of HPV31 E5 oncogene in cervical scraping samples from Brazilian women to assess their functional and structural effects, in order to identify possible repercussions of these variants on the infectious and carcinogenic process. Our results detected nucleotide changes previously described in the HPV31 E5 oncogene, which may play a critical role in the development of cancer due to its ability to promote cell proliferation and signal transmission. In our study, the interaction percentage of the 31E5 sequence generated by the Immune Epitope Server database and the Analysis Resource (IEDB) allowed us to include possible immunogenic epitopes with the MHC-I and MHC-II molecules, which may represent a possible relationship between protein suppression of the immune system. In the structural analysis of the HPV31 E5 oncoprotein, the N5D, I48 V, P56A, F80I and V64I polymorphisms can be found inserted within transmembrane regions. The P56A mutation has been predicted to be highly stabilizing and, therefore, can cause a change in protein function. Regarding the interaction of the E5 protein from HPV31 with the signaling of NF-kB pathway, we observed that in all variants of the E5 gene from HPV-31, the activity of the NF-kB pathway was increased compared to the prototype. Our study contributes to a more refined design of studies with the E5 gene from HPV31 and provides important data for a better understanding of how variants can be distinguished under their clinical consequences.

Functional evaluation of human papillomavirus type 31 long control region variants.

Persistent infections by high-risk human papillomavirus (HR-HPV) are a necessary condition, but not sufficient for cervical cancer development. Genetic variants of HR-HPV appear to be related to the risk of persistent infections. The study performed a functional evaluation of variants of the HPV-31 promoter region (LCR). For this, cloning and subcloning of variants HPV-31/UFPE-21 HPV-31/UFPE-89, HPV-31/UFPE-66, E2 gene and prototype HPV-31 were performed. Transfection with different concentrations of E2 was done and the concentration of 25 ng was determined to be ideal for LCR activation. HPV-31/UFPE-21 and HPV-31/UFPE-89 have a greater ability to alter Nluc reporter gene expression levels and HPV-31/UFPE-66 showed decreased levels of gene expression of Nluc reporter gene compared to control. Statistical analysis showed a significant difference between the polymorphic LCR regions and the control (p < 0.0001). A more refined profile of variants of HPV-31 and its importance for the prognosis of cervical lesions begins to be drawn.

Short communication: Effect of supplemental zinc source with and without evaporative cooling on systemic and mammary metabolism of lactating dairy cows during summer.

The negative effects of heat stress partly result from disturbed systemic metabolic responses and possibly altered mammary gland metabolism of lactating dairy cows. Our previous research reported that supplemental dietary Zn sources may affect milk fat synthesis of lactating cows during summer. Thus, our objective was to evaluate the systemic and mammary metabolism of cows fed 2 supplemental Zn sources under 2 environmental conditions. Multiparous lactating Holstein cows (n = 72; days in milk: 99.7 ± 13.4 d; parity: 2.9 ± 0.3) were randomly assigned to 4 treatments in a 2 × 2 factorial arrangement. Treatments included 2 different environments: cooled (CL) using fans and misters or noncooled (NC), and 2 supplemental Zn sources: 75 mg of Zn hydroxychloride/kg of DM (IOZ) or 35 mg of Zn hydroxychloride/kg of DM + 40 mg of Zn-Met complex/kg of DM (ZMC). The 168-d experiment was divided into baseline and environmental challenge phases, 84 d each. During the baseline phase, all cows were cooled and fed respective dietary treatments, and during the environmental challenge phase cows continued receiving the same diets but NC cows were deprived of cooling. Temperature-humidity index averaged 77.6 ± 3.8 and 77.8 ± 3.8 for CL and NC pens, respectively, during the environmental challenge phase. Plasma was collected before the baseline phase and at 1, 3, 5, 12, 22, 26, 41, 54, 61, 68, 75, and 81 d of the environmental challenge phase for metabolites and insulin analyses. Mammary biopsies were collected before the baseline phase and at 7 and 56 d of the environmental challenge phase to measure mRNA abundance of proteins related to mammary metabolism. Compared with CL, NC reduced plasma glucose, nonesterified fatty acids, ß-hydroxybutyrate, and triglyceride concentrations, but increased insulin concentration. Cows fed ZMC had greater plasma triglyceride concentration than IOZ. Treatments had no effect on mRNA abundance of protein related to mammary fatty acid and glucose metabolism except that NC cows had greater mammary mRNA abundance of 6-phosphogluconate dehydrogenase and ATP-dependent 6-phosphofructokinase than CL cows. In conclusion, deprivation of evaporative cooling influenced the metabolism of lactating dairy cows but dietary Zn source had no apparent effect.

Jaburetox, a urease-derived peptide: Effects on enzymatic pathways of the cockroach Nauphoeta cinerea.

Jaburetox is a recombinant peptide derived from one of the Canavalia ensiformis urease isoforms. This peptide induces several toxic effects on insects of different orders, including interference on muscle contractility in cockroaches, modulation of UDP-N-acetylglucosamine pyrophosphorylase (UAP) and nitric oxide synthase (NOS) activities in the central nervous system of triatomines, as well as activation of the immune system in Rhodnius prolixus. When injected, the peptide is lethal for R. prolixus and Triatoma infestans. Here, we evaluated Jaburetox toxicity to Nauphoeta cinerea cockroaches, exploring the effects on the central nervous system through the activities of UAP, NOS, acid phosphatases (ACP), and acetylcholinesterase (AChE). The results indicated that N. cinerea is not susceptible to the lethal effect of the peptide. Moreover, both in vivo and in vitro treatments with Jaburetox inhibited NOS activity, without modifying the protein levels. No alterations on ACP activity were observed. In addition, the enzyme activity of UAP only had its activity affected at 18 hr after injection. The peptide increased the AChE activity, suggesting a mechanism involved in overcoming the toxic effects. In conclusion, our findings indicate that Jaburetox affects the nitrinergic signaling as well as the AChE and UAP activities and establishes N. cinerea as a Jaburetox-resistant model for future comparative studies.

Vulnerability of the micro-regions of the South of Brazil to the new coronavirus (SARS-CoV-2) pandemic / Vulnerabilidade das microrregiões da Região Sul do Brasil à pandemia do novo coronavírus (SARS-CoV-2)

This is the first report of the 'Observatório COVID191 - Grupo: Redes de Contágio ­ Laboratório de Estudos de Defesa' for the South region of Brazil. We have combined data of confirmed cases of the new coronavirus (SARS-CoV-2) for the South available up to 17/04/2020, with structural analyses of road networks, from within and between states, to estimate the vulnerability and potential influence of the South micro-regions to propagate the disease.

Este é o primeiro relatório do Observatório COVID19 - Grupo: Redes de Contágio ­ Laboratório de Estudos de Defesa para a região Sul do Brasil. Combinamos dados de casos confirmados do novo coronavírus (SARS-CoV-2) para o Sul, disponíveis até o dia 17/04/2020, com análises estruturais da rede de rotas rodoviárias intra e interestaduais para estimarmos a vulnerabilidade e potencial influência das microrregiões sulinas na propagação da doença.

Triethylphosphinegold(I) Complexes with Secnidazole-Derived Thiosemicarbazones: Cytotoxic Activity against HCT-116 Colorectal Cancer Cells under Hypoxia Conditions.

Triethylphosphinegold(I) complexes [Au(HL1)P(CH2CH3)3]PF6 (1), [Au(HL2)P(CH2CH3)3]PF6 (2), and [Au(HL3)P(CH2CH3)3]PF6 (3) were obtained with (E)-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)hydrazinecarbothioamide (HL1), (E)-N-methyl-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)hydrazinecarbothioamide (HL2), and (E)-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)-N-phenylhydrazinecarbothioamide (HL3). All compounds were assayed for their cytotoxic activities against HCT-116 colorectal carcinoma cells under normoxia and hypoxia conditions and against nonmalignant HEK-293 human embryonic kidney cells under normoxia conditions. The thiosemicarbazone ligands HL1-HL3 were inactive against HCT-116 cells under hypoxia but while HL3 was inactive, HL1 and HL2 proved to be cytotoxic to both cell lineages under normoxia conditions. Complexes (1-3) and the triethylphosphinegod(I) precursor proved to be active against both cell lineages in normoxia as well as in hypoxia. While 1 and 3 revealed to be active against HEK-293 and HCT-116 cells, being approximately as active against HCT-116 cells in normoxia as under hypoxia, complex (2) proved to be more active against HCT-116 cells under hypoxia than under normoxia conditions, and more active against HCT-116 cells than against the nonmalignant HEK-293 cells, with the selectivity index, calculated as SI = IC50HEK-293/IC50HCT-116hypoxia, equal to 3.7, similar to the value obtained for the control drug tirapazamine (tirapazamine (TPZ), SI = 4). Although the compounds showed distinct cytotoxic activities, the electrochemical behaviors of HL1-HL3 were very similar, as were the behaviors of complexes (1-3). Complex (2) deserves special interest since it was significantly more active under hypoxia than under normoxia conditions. Hence, in this case, selective reduction of the nitro group in a low oxygen pressure environment, resulting in toxic reactive oxygen species (ROS) and damage to DNA or other biomolecules, might operate, while for the remaining compounds, other modes of action probably occur.

Pediatric multiple sclerosis: from clinical basis to imaging spectrum and differential diagnosis.

Pediatric multiple sclerosis (MS) deserves special attention because of its impact on cognitive function and development. Although knowledge regarding pediatric MS has rapidly increased, understanding the peculiarities of this population remains crucial for disease management. There is limited expertise about the efficacy and safety of current disease-modifying agents. Although pathophysiology is not entirely understood, some risk factors and immunological features have been described and are discussed herein. While the revised International Pediatric MS Study Group diagnostic criteria have improved the accuracy of diagnosis, the recently revised McDonald criteria also offer some new insights into the pediatric population. It is fundamental that radiologists have strong knowledge about the vast spectrum of demyelinating disorders that can occur in childhood to ensure appropriate diagnosis and provide early treatment.

Nonpharmacological analgesic interventions among newborn infants in the University Hospital of the University of Sao Paulo: a best practice implementation project.

INTRODUCTION: Despite evidence from studies on nonpharmacological pain management among newborns, many health professionals still don't apply evidence from scientific knowledge in their clinical practice. OBJECTIVES: To promote evidence-based practice for nonpharmacological analgesic interventions among newborns in the Maternity Ward of the University Hospital of the University of Sao Paulo, improving pain management and promoting healthy newborn growth and development, and better use of resources. METHOD: The current evidence implementation project used the JBI Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback tool. The JBI Practical Application of Clinical Evidence System and Getting Research into Practice framework for promoting evidence-based healthcare involve three phases of activity: conducting a baseline audit, implementing strategies to address areas of noncompliance and conducting a follow-up audit to assess the outcomes of the interventions implemented to improve practice. Ten evidence-based criteria on nonpharmacological pain management among newborns were audited, by direct observation of the nursing staff activities involving single skin-breaking procedures in the newborn. RESULTS: The baseline audit indicated poor compliance with evidence in current practice in most of the evidence-based criteria audited. Discussion with the implementation team identified barriers to best practice, with interventions including a nursing protocol and educational program for all nursing staff on nonpharmacological analgesic approaches to reduce pain in the newborn (breastfeeding, skin-to-skin contact with the mother, nonnutritive sucking and glucose 25%), and a leaflet to inform the best available evidence on newborn pain management. In the follow-up audit, compliance increased in eight of nine audit criteria, with criterion 7 remaining at 100% compliance to best practice. CONCLUSION: The current best practice implementation project contributed to establishing evidence-based practice and enhancing neonatal pain management during skin-breaking painful procedures in the University Hospital. However, to achieve 100% compliance with all the evidence-based audit criteria, we will need to invest in continuing education and extend this implementation project to other related settings of the hospital. Moreover, it is necessary to perform follow-up cyclical audits to assess compliance and address barriers to best practice, enhancing the quality of nursing care, ensuring better results on pain management of the newborn and ongoing sustainability of this project.

The role of kinin B1 and B2 receptors in the mouse model of oxazolone-induced atopic dermatitis.

This study evaluated the role of kinin B1 and B2 receptors in the pre-clinical mouse model of oxazolone-induced atopic dermatitis. The B1 R715 or B2 HOE140 receptor antagonists were dosed at different schemes of treatment. After assessment of clinical lesion scores and pruritus, lesional skin samples were collected for histopathological analysis. The plasma extravasation and the expression of the metalloproteinase ADAMTS5 were also assessed. The immunopositivity for kinin receptors was evaluated in the skin, dorsal root ganglion (DRG), thoracic spinal cord and brain cortex sections. Marked upregulation of B1 and B2 receptors was observed in the skin of oxazolone-treated mice. The induction of atopic dermatitis led to a downregulation of both receptors in the DRG, without any alteration in the spinal cord and brain cortex. The repeated administration of HOE140 (50 nmol/kg; i.p.) partially inhibited the oxazolone-related pruritus, associated with a reduction of ADAMTS5 immunolabelling in the skin. Alternatively, R715 (438 nmol/kg; i.p.) produced a mild inhibition of plasma extravasation in oxazolone-challenged mice. Noteworthy, the repeated i.d. injection of R715 (30 nmol/site) or HOE140 (3 nmol/site) significantly reduced the histiocyte numbers, according to the histopathological analysis. Either B1 or B2 kinin antagonists, irrespective of the protocol of treatment, did not alter any other evaluated clinical or histological parameters. Data brings novel evidence about the role of kinin receptors in allergy-related conditions, such as atopic dermatitis. Further studies to test different protocols of treatment with kinin antagonists on in-depth cellular alterations underlying oxazolone-induced atopic dermatitis remain to be performed.

Structural studies and antileishmanial activity of 2-acetylpyridine and 2-benzoylpyridine nitroimidazole-derived hydrazones.

Three imidazole hydrazone compounds, namely 2-(4-nitro-1H-imidazol-1-yl)-N'-[1-(pyridin-2-yl)ethylidene]acetohydrazide, C12H12N6O3, (1), 2-(2-nitro-1H-imidazol-1-yl)-N'-[1-(pyridin-2-yl)ethylidene]acetohydrazide, C12H12N6O3, (2), and 2-(2-nitro-1H-imidazol-1-yl)-N'-[(phenyl)(pyridin-2-yl)methylidene]acetohydrazide, C17H14N6O3, (3), were obtained and fully characterized, including their crystal structure determinations. While all the compounds proved not to be cytotoxic to J774.A1 macrophage cells, (1) and (3) exhibited activity against Leishmania chagasi, whereas (2) was revealed to be inactive. Since both (1) and (3) exhibited antileishmanial effects, while (2) was devoid of activity, the presence of the acetyl or benzoyl groups was possibly not a determining factor in the observed antiprotozoal activity. In contrast, since (1) and (3) are 4-nitroimidazole derivatives and (2) is a 2-nitroimidazole-derived compound, the presence of the 4-nitro group probably favours antileishmanial activity over the 2-nitro group. The results suggested that further investigations on compounds (1) and (3) as bioreducible antileishmanial prodrug candidates are called for.