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Abstract Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID). Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator’s bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies’ quality and level of bias. Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators. Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.

Abstract Currently, there is a demand for protein sources that do not use soil management or animal breeding. Among these sources we highlight the microorganisms, such cyanobacteria and microalgae, which have a simple growth using light, CO2, water and some mineral salts to generate high protein production. The extraction of these proteins depends on the method used. The most used methods for extracting bio-functional proteins are mechanical, chemical and enzymatic. The aim of this work is to analyze the protein extraction methods in microalgae using Scielo, ScienceDirect and NCBI (PubMed) electronic databases that made it possible to select original studies published in the last five years (2018-2023). A total of 2707 articles, 25 of which were selected for further analysis and subjected to risk of bias assessment. The genera Chlorella, Scenedesmus and Nannochloropsis were the most studied due to their high protein content. Mechanical methods and chemical hydrolysis are the most used methods, achieving an extraction yield of 46.0 % and 64.0 %, respectively. The best extraction results are obtained with a combination of methods, reaching up to 80.0 % yield. However, some aspects need to be observed to choose an ideal protein extraction method.

Abstract Cardiovascular diseases, resulting from the deposition of clots in blood vessels, are the leading cause of death worldwide. Fibrinolytic enzymatic activity can catalyze blood clot degradation. Findings show that 36 fungal isolates recovered from Caatinga soils have the potential to produce fibrinolytic protease under submerged conditions. About 58 % of the isolates displayed fibrinolytic activity above 100 U/mL, with Mucor subtilissimus UCP 1262 being the most active. The protease was biochemically and biophysically characterized, showing that the enzyme had a high affinity for SAApNA substrate and was significantly inhibited by fluoride methyl phenyl sulfonyl-C7H7FO2S, suggesting that it is a chymotrypsin-like serine protease. The highest enzyme activity was detected at pH 5.0 and 28 °C. This fibrinolytic protease’s far-UV circular dichroism (CD) showed that its secondary structure was primarily α-helical. The purified fibrinolytic enzyme may represent a novel therapeutic agent for treating thrombosis. At temperatures above 65 °C, the enzyme lost all its secondary structure. Its melting temperature was 58.1 °C, the denaturation enthalpy 85.1 kcal/mol, and the denaturation entropy 0.26 kcal/K∙mol.

BackgroundAnhedonia refers to the diminished capacity to experience pleasure. It has been described both as a symptom of depression and an enduring behavioral trait that contributes its development. Specifically, in stroke patients, anhedonia has been closely linked to depression, resulting in reduced sensitivity to everyday pleasures and intrinsic motivation to engage in rehabilitation programs and maintain a healthy active lifestyle. This condition may hinder patients’ recovery, diminishing their autonomy, functioning, and quality of life.ObjectiveWe aimed to explore the prevalence and level of anhedonia and those variables that might be associated in patients with both ischemic and hemorrhagic stroke at subacute and chronic phases of the disease.MethodsWe conducted an exploratory cohort study with a sample of 125 patients with subacute and chronic stroke presenting upper-limb motor deficits. We measured participants’ level of anhedonia with four items from the Beck Depression Inventory-II that describe the symptoms of this condition: loss of pleasure, loss of interest, loss of energy, and loss of interest in sex. We also collected demographic and clinical information and evaluated motor and cognitive functions as well as levels of depression, apathy, and various mood states. The results were compared to a sample of 71 healthy participants of similar age, sex, and level of education.ResultsStroke patients demonstrated a significantly higher prevalence (18.5–19.7%) and level of anhedonia compared to the healthy controls (4.3%), regardless of stroke phase, level of motor impairment, and other clinical variables. Furthermore, post-stroke anhedonia was associated with lower levels of motivation and higher levels of negative mood states such as fatigue and anger in the long term. Importantly, anhedonia level was superior in stroke patients than in healthy controls while controlling for confounding effects of related emotional conditions.ConclusionThis study provides novel evidence on the prevalence, level and factors related to anhedonia post-stroke. We emphasize the importance of assessing and treating anhedonia in this population, as well as conducting large-scale cohort and longitudinal studies to test its influence on long-term functional and emotional recovery.

Introdução: A Doença Hemolítica Feto e Recém-Nascido (DHFRN), se caracteriza por um quadro de destruição das hemácias fetais e/ou do Recém-Nato (RN) devido a presença de Anticorpos (Ac) IgG maternos que atravessam a barreira placentária e se ligam a antígenos de herança paterna presentes nas hemácias fetais ou do RN provocando sensibilização e hemólise. Estes anticorpos podem ser naturais (sistema ABO) ou imunes (Sistemas Rh, K, JK, etc.) adquiridos por transfusões ou gestações anteriores ou devido a sangramento feto-materno em gestação atual. O grau de hemólise e o quadro clínico da DHFRN é multifatorial. Na Incompatibilidade Rh (D) as consequências clínicas são mais exuberantes. Na incompatibilidade ABO o mais comum é por mãe O+ e RN A+ e de uma forma geral o quadro clínico é leve e muitas vezes assintomático. Relato de caso: RN a termo, 38 semanas, peso 2785g, nascido de parto vaginal, Apgar 9/9. Com 13 horas de vida apresenta icterícia com BT = 16,8 mg/dL, BI = 14,9 mg/dL, Ht = 34,9% e Hb = 11,6 g/dL quando iniciada a fototerapia tríplice. Segue com piora clínica, apresenta letargia e queda do Ht que chega a 24% no D3. Iniciada a investigação de hemólise imunológica. Grupo sanguíneo (GS) materno O+, Pesquisa de anticorpos Irregulares (PAI) negativa. GS paterno AB+. Dados do RN: GS A+, Teste da antiglobulina Humana direto (TAD) 1+. Para caracterizar o anticorpo presente nas hemácias do RN, foi realizada eluição direta e testado o eluato em Cartão Gel/Liss/Coombs com as hemácias de Triagem I, II e hemácias A1 e B. O resultado do teste com hemácias de Triagem I e II foi negativo e com hemácias A1 e B 4+. Discussão: A PAI materna é negativa o que exclui a incompatibilidade por grupos sanguíneos diferentes do ABO. O TAD+ do RN demonstra a possibilidade de hemólise imunológica. O teste de eluição direta a partir das hemácias fetais foi positiva apenas com hemácias A1 e B e demonstra que o anticorpo eluído é anti-AB. Realizado então a titulação do anticorpo anti-AB no plasma materno e o título foi 1024. Indivíduos do grupo O apresentam anticorpos anti-AB que se ligam tanto a hemácias A quanto B. Estes resultados caracterizam quadro de Incompatibilidade ABO. O título do anticorpo ABO materno é extremamente alto. Foge a média encontrada em doadores de sangue do grupo O que é de 128. Isto justifica o quadro clínico importante no RN. O RN é A+ mas devido a presença do anti-AB materno no seu plasma deve ser transfundido com Concentrado de Hemácias (CH) do grupo O. O RN recebeu 1 CH O+ com ótimo aproveitamento e seguiu em fototerapia. No D9 embora ainda com TAD+ fraco, Ht = 38%, Hb = 13,4 g/dL e BT = 3 mg/dL, BI = 2,8 mg/dL. Conclusão: Em geral, a hemólise imunológica só é investigada em gestantes e/ou puérperas Rh (D) negativas. É importante ter em mente que outros sistemas eritrocitários podem estar associados a quadros de DHFRN. Na exclusão da doença por anticorpos relacionados a outros sistemas, a incompatibilidade ABO deve ser investigada para que o suporte transfusional a estes RN possa se dar realizado adequadamente através da seleção do CH negativo para o antígeno correspondente ao anticorpo materno.

O Suporte Transfusional (ST) a pacientes com grupo sanguíneo raro (frequência ≤1:000) é um desafio em especial se o paciente apresentar doenças crônicas com alta demanda transfusional como a Doença Falciforme (DF). Pacientes com DF podem ser negativos para Antígenos (Ag) de alta frequência de diversos Sistemas entre eles o MNS (S-s-U-). Recomenda-se que estes pacientes sejam transfundidos de acordo considerando seu fenótipo ABO, D, C, c, E, e, K e para os Ag relacionados a presença de Anticorpos (Ac). Não existe nenhuma diretriz para prevenção da aloimunização em pacientes com fenótipos raros. O objetivo deste trabalho é avaliar o ST a 3 pacientes S-s-U- com DF matriculados no HEMORIO. Material e métodos: Foram avaliados sexo, idade, grupo sanguíneo, fenotipagem eritrocitária, número (N) de Concentrado de Hemácias (CH) U+ e U- transfundidas, Ac eritrocitários detectados na Pesquisa de Anticorpos Irregulares (PAI) e N de transfusões até o aparecimento do anti-U. Resultados: Paciente 1: JMS, 31 anos, sexo masculino (M), O+, C+, c+, E+, e+, K-, recebeu 61 CH U+ e até o presente tem PAI-. Paciente 2: RO, 30 anos sexo feminino (F), O+, C-, c+, E+, e+, K-, recebeu 204 CH U+. Após a transfusão de 2 CH U+ apresentou PAI+ devido a presença de Autoanticorpo (AAc) IgG, quente e público. A presença de anti-U foi descartada. Após transfusão de 85 CH desenvolveu anti-C. Manteve a PAI+ em vários momentos devido a AAc. Todos os CH transfundidos foram U+. Paciente 3: AEJD, 11 anos, sexo F, B+, C-, c+, E-, e+, K-, recebeu 8 CH U+. Após a transfusão de 4 CH U+ apresentou PAI+ devido a anti-U. Em 2023, apresentou alta demanda transfusional sendo necessário mobilizar doadores U-. Foram transfundidos 4 CH, 1 proveniente do HEMORIO, 1 do Hemonúcleo de Macaé e 2 através do Cadastro Nacional de Sangue Raro (CNSR) sendo 1 doador do HEMOCE e 1 da UNICAMP. Para o ST destes pacientes foram necessários 273 CH desleucocitados e fenotipados para Rh+K. Discussão: O paciente 1 não desenvolveu Ac. A paciente 2 desenvolveu anti-C, embora todos os CH fossem C- o que levanta hipótese de erro na fenotipagem de algum CH transfundido. Apenas a paciente 3 desenvolveu anti-U. É a paciente mais jovem (11 anos) e que recebeu apenas 4 CH até o aparecimento do anti-U. Os dados demonstram que a aloimunização é uma condição multifatorial e não só restrita N de transfusões. A demanda transfusional destes pacientes em 2023 foi de 14 CH. Sendo necessários 4 CHU- para a paciente 3. O HEMORIO conta apenas com 4 doadores S-s-U- confirmados por biologia molecular sendo 1 A+, 1 B- e 2 O+. Existem outros doadores cadastrados aguardando a confirmação molecular. No CNSR há registro de 23 doadores S-s-U- e 21 doadores S-s-U variante independente de grupo ABO/D. Por não dispormos de unidades U- congeladas houve atrasos no atendimento a paciente 3 devido a dificuldade na logística de convocação dos doadores, liberação dos testes sorológicos e transporte dos CH. Dos 3 pacientes 2 são do sexo feminino (pacientes 2 e 3). Ac anti-U estão relacionados a Doença Hemolítica do Feto e Recém Nascido (DHFRN). A paciente 2 está em idade fértil e ações preventivas através da transfusão somente de CH U- merecem ser avaliadas. A paciente 3 já tem seu futuro gestacional comprometido pela presença do anti-U. Conclusão: O CNSR é plenamente eficiente na disponibilidade de sangue U-. Um banco de CH criopreservados proporcionaria um atendimento mais rápido e eficaz no ST a estes pacientes.

Background Chronic non-cancer pain (CNCP) treatment’s primary goal is to maintain physical and mental functioning while improving quality of life. Opioid use in CNCP patients has increased in recent years, and non-pharmacological interventions such as music listening have been proposed to counter it. Unlike other auditive stimuli, music can activate emotional-regulating and reward-regulating circuits, making it a potential tool to modulate attentional processes and regulate mood. This study’s primary objective is to provide the first evidence on the distinct (separate) effects of music listening as a coadjuvant maintenance analgesic treatment in CNCP patients undergoing opioid analgesia.Methods and analysis This will be a single-centre, phase II, open-label, parallel-group, proof-of-concept randomised clinical trial with CNCP patients under a minimum 4-week regular opioid treatment. We plan to include 70 consecutive patients, which will be randomised (1:1) to either the experimental group (active music listening) or the control group (active audiobooks listening). During 28 days, both groups will listen daily (for at least 30 min and up to 1 hour) to preset playlists tailored to individual preferences.Pain intensity scores at each visit, the changes (differences) from baseline and the proportions of responders according to various definitions based on pain intensity differences will be described and compared between study arms. We will apply longitudinal data assessment methods (mixed generalised linear models) taking the patient as a cluster to assess and compare the endpoints’ evolution. We will also use the mediation analysis framework to adjust for the effects of additional therapeutic measures and obtain estimates of effect with a causal interpretation.Ethics and dissemination The study protocol has been reviewed, and ethics approval has been obtained from the Bellvitge University Hospital Institutional Review Board, L’Hospitalet de Llobregat, Barcelona, Spain. The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration number NCT05726266.

Limited information is available regarding the role of anaerobic metabolism capacity on GOLD 1 and 2 COPD patients during upper limb exercise. We aimed to compare the upper limb anaerobic power capacity, blood lactate concentration, cardiovascular and respiratory responses, in male COPD patients versus healthy subjects during the 30-s Wingate anaerobic test (WAnT). The rate of fatigue and time constant of the power output decay (τ, tau) were also calculated and a regression analysis model was built to assess the predictors of τ in these patients. Twenty-four male COPD patients (post-bronchodilator FEV1 73.2 ± 15.3% of predicted) and 17 healthy subjects (FEV1 103.5 ± 10.1% of predicted) underwent the WAnT. Measurements were performed at rest, at the end of the WAnT, and during 3′ and 5′ of recovery time. Peak power (p = 0.04), low power (p = 0.002), and mean power output (p = 0.008) were significantly lower in COPD patients than in healthy subjects. Power output decreased exponentially in both groups, but at a significantly faster rate (p = 0.007) in COPD patients. The time constant of power decay was associated with resistance (in ohms) and fat-free mass (r2 = 0.604, adjusted r2 = 0.555, and p = 0.002). Blood lactate concentration was significantly higher in healthy subjects at the end of the test, as well as during 3′ and 5′ of recovery time (p

Abstract A fibrinolytic enzyme from the microalga Dunaliella tertiolecta was produced under mixotrophic conditions using different corn steep liquor (CSL) concentrations ( 0 ≤ CLS ≤ 0.75%), purified using a combination of salting out and ion-exchange chromatography, and then biochemical characterized. Cultivation of this microalga using 0.5% CSL led to the highest maximum cell concentration (1.960±0.010 mg L-1) and cell productivity (0.140g L-1 day-1), besides a high fibrinolytic activity of the extract obtained by the homogenization method (102 ±1 U mL-1). The enzyme extracted from the microalgal biomass was 5-fold purified with a 20% yield and was found to have a specific activity of 670 U mg-1. The enzyme, whose molecular weight determined by fibrin zymography was 10 kDa, was shown to be stable at pH 3.0–9.0 and up to 70°C with optimal pH and temperature values of 8.0 and 50°C, respectively. When compared to other fibrinolytic enzymes, this protease stood out for its high fibrinolytic activity, which was enhanced by Fe2+, inhibited by Zn2+, Cu2+, Mg2+, and Ca2+, and strongly inhibited by phenylmethylsulfonyl fluoride, suggesting that it belongs to the serine metalloprotease family. Moreover, thanks to its thermal stability, the enzyme may be easily preserved and activated under high-temperature conditions.

Abstract INTRODUCTION The effects of COVID‐19 confinement have been severe, especially in older adults. Therefore, we analyzed the factors associated with cognitive impairment (CI) in Latin America (LA). METHODS We conducted a cross‐sectional observational study with a total of 5245 older adults from 10 countries in LA. Measurement We used the Telephone Montreal Cognitive Assessment (T‐MoCA) and the Eight‐item Informant Interview to Differentiate Aging and Dementia (AD8) scale. RESULTS We found that age, depressive symptomatology, bone fractures, being widowed, having a family member with dementia, and unemployment were associated with an increased risk of CI. In contrast, higher education, hypertension with continuous treatment, quarantine, and keeping stimulating cognitive and physical activities were associated with a lower probability of CI. No significant association was found between suffering from diabetes or being retired and CI. DISCUSSION It is essential to conduct follow‐up studies on these factors, considering their relationship with CI and the duration of confinement.

Senotherapeutic molecules decrease cellular senescence burden, constituting promising approaches to combat the accumulation of senescent cells observed in chronological aging and age-related diseases. Numerous molecules have displayed senotherapeutic potential, but toxicity has been frequently observed. Recently, a new senotherapeutic compound, Peptide 14, was developed to modulate cellular senescence in the skin. In order to assess the potential toxic and genotoxic effects of the peptide, we observed the viability of human primary dermal fibroblasts and epidermal keratinocytes with Peptide 14 treatment, and show that it is mostly non-toxic in concentrations up to 100 μM. Cancer lines were also used to investigate its potential of modulating proliferation. Different concentrations of the peptide promoted a discrete reduction in the proliferation of cancerous cells of the MeWo and HeLa lineages. In full-thickness human skin equivalents, topically formulated Peptide 14 also failed to exert any significant irritation, nor cellular toxicity when added to the culture media. Genotoxic assays including the Ames, micronucleus, and karyotyping tests also indicate the safety of the peptide. Finally, the irritative potential of the peptide was assessed in human subjects in a repeated insult patch test executed using 1 mM peptide. No visible skin reactions were observed in any of the 54 participants. Taken together, the present data support that Peptide 14 is a senotherapeutic molecule with a positive safety profile as tested with cruelty-free models, justifying further studies involving the peptide.

Bovine colostrum is a rich source of nutrients and biologically active molecules known to be able to modulate the human immune system, such as lactoferrin, lysozyme, lactoperoxidase, immunoglobulins and growth factors. This comprehensive review aimed to gather evidence from animal experimentation and clinical trials that investigated the potential effects of bovine colostrum in preventing and treating diseases that affect the human gastrointestinal tract. Considered safe for human consumption, BC or its isolate components were used against a range of different gastrointestinal disorders. Beneficial effects were observed in several conditions: gastrointestinal infections, infectious diarrhoea, drug-induced lesions, gut-barrier malfunction, and inflammatory bowel disease. Under proper processing to maintain its components' integrity, BC products are valuable supplements with high nutraceutical value, capable of promoting and restoring gastrointestinal health.

Abstract This study aims to evaluate the in silico genomic characteristics of Streptococcus infantarius subsp. infantarius, isolated from Coalho cheese from Paraíba, Brazil, with a view to application in lactic fermentations. rRNA sequences from the 16S ribosomal region were used as input to GenBank, in the search for patterns that could reveal a non-pathogenic behavior of S. infantarius subsp. infantarius, comparing mobile genetic elements, antibiotic resistance genes, pan-genome analysis and multi-genome alignment among related species. S. infantarius subsp. infantarius CJ18 was the only complete genome reported by BLAST/NCBI with high similarity and after comparative genetics with complete genomes of Streptococcus agalactiae (SAG153, NJ1606) and Streptococcus thermophilus (ST106, CS18, IDCC2201, APC151) revealed that CJ18 showed a low number of transposases and integrases, infection by phage bacteria of the Streptococcus genus, absence of antibiotic resistance genes and presence of bacteriocin, folate and riboflavin producing genes. The genome alignment revealed that the collinear blocks of S. thermophilus ST106 and S. agalactiae SAG153 have inverted blocks when compared to the CJ18 genome due to gene positioning, insertions and deletions. Therefore, the strains of S. infantarius subsp. infantarius isolated from Coalho cheese from Paraíba showed genomic similarity with CJ18 and the mobility of genes analyzed in silico showed absence of pathogenicity throughout the genome of CJ18, indicating the potential of these strains for the dairy industry.

Abstract Hypertension is a factor that contributes to the risk of chronic diseases. The inhibition of angiotensin-I converting enzyme (ACE) is a useful therapeutic approach to the hypertension treatment. The algae have been an alternative for the production of ACE inhibitory (ACEi) peptides from enzymatic hydrolysis due to their protein-rich biomass. The aim of this study was to systematically review the literature regarding the production, composition and activity of ACEi peptides derived from algae proteins. Systematic database searches identified 648 related articles. Among these, only 14 were selected according to the eligibility criteria to this review. Macroalgae are more studied than microalgae as sources of ACEi peptides. Furthermore, hydrolysates by thermolysin or bromelain exhibited the highest ACEi activity compared to other enzymes. The main features of the peptides with high ACE inhibition are low molecular weight, short amino acids sequence and non-competitive inhibition pattern. In vivo studies using hydrolysates and peptides derived from algae proteins showed antihypertensive activity in spontaneously hypertensive rats (SHR). Thus, it is suggested that ACEi peptides derived from algae can be considered as potential antihypertensive.

Fall-related causes in patients with COPD might be associated to functional balance impairments and greater disease severity. We aimed to evaluate the reasons for falls in patients with COPD who had presented any fall during the previous year. This is a cross-sectional study. All COPD’s GOLD classifications (mild, moderate, severe, and very severe) patients were recruited. In order to participate, patients ought to be clinically stable and without any exacerbation within 30 days prior to study entry. History of falls was self-reported by patients through an interview. Pre and post bronchodilator (salbutamol 400 μg) spirometry was performed. All patients accomplished postural balance tests such as the Berg Balance Scale, Falls Efficacy Scale-International, Time up and Go, Functional Reach test, Tinetti test and Chalder Scale; furthermore, lower limbs muscle strength (muscle dynamometry) and the COPD Assessment Test (CAT) were assessed. Ninety-six patients with COPD were evaluated and divided into two groups stratified according to any positive history of falls in the previous year. Patients with COPD who had any fall in the previous year presented older age (p=0.01), higher BMI (p=0.04) and worse pulmonary function than those who did not fall. The risk of falls was increased in patients with lower muscle strength in the lower limbs (OR 2.9, CI 95%;1.6 to 3.9), age greater than 65 years (OR 2.7, CI 95%;1.3 to 3.4), BMI greater than 28.8 kg/m2 (OR 3.2, CI 95%;1.1 to 5.6), very severe airway obstruction (OR 3.9, CI 95%;2.2 to 3.9) and fatigue (OR 3.2, CI 95%;1.5 to 5.3). Impaired body balance, reduced lower limb strength, disease severity, presence of fatigue and elevated BMI are important factors for falls in patients with COPD.

Background The impact of quarantine in older adults have been reported in several studies with contradictory results, reporting from negative effects to no significant outcomes or even beneficial consequences. Heterogeneity in aging plays a role in each region, the aim of this study is to analyze the impact of quarantine on health conditions (physical and mental) and lifestyle in older adults in five Centro American countries during COVID-19 pandemic. Method In this cross-sectional study, n = 712 older adults 60 years and older from Mexico, Guatemala, El Salvador, Honduras and Costa Rica were assessed by telephone. Sociodemographic data, physical and mental health, lifestyle and quarantine conditions were asked previous informed consent. Results In general, mean of days in quarantine at the moment of the study was 142 days (approximately four months and three weeks). In the analysis of the impact of the days in quarantine effects were found on the frequency of falls, functional ability in Activities of Daily Living (ADL), general cognitive function, memory, orientation, language, frequency of drinking alcohol, having a balanced diet, and being active cognitively. Some differences were found between countries. Conclusions Effects of quarantine on older adults in Centro America, requires attention of governments and healthcare to prevent long term morbidity and disability, and to promote healthy aging.

Characterizing the cyclic magnetic activity of stars that are close approximations of our Sun offers our best hope for understanding our Sun’s current and past magnetism, the space weather around solar-type stars, and more generally, the dynamos of other cool stars. The nearest current approximation to the Sun is the solar twin 18 Scorpii, a naked-eye Sun-like star of spectral type G2 Va. However, while 18 Scorpii’s physical parameters closely match those of the Sun, its activity cycle is about 7 yr, and shorter than the solar cycle. We report the measurement of a periodicity of 15 yr that corresponds to a longer activity cycle for 18 Scorpii based on observations extending to the last three decades. The global magnetic geometry of 18 Scorpii changes with this 15 yr cycle and appears to be equivalent to the solar 22 yr magnetic polarity cycle. These results suggest that 18 Scorpii is also a magnetic proxy for a younger Sun, adding an important new datum for testing dynamo theory and magnetic evolution of low-mass stars. The results perturb our understanding of the relationship between cycle and rotation, constrain the Sun’s magnetism and the Sun–Earth connection over the past billion years, and suggest that solar Schwabe and Hale cycle periods have increased over that time span.

Abstract Fibrinolytic proteases are a promising alternative in the pharmaceutical industry, they are used in the treatment of cardiovascular diseases, especially thrombosis. Microorganisms are the most interesting source of fibrinolytic proteases. The aim of this study was the production of fibrinolytic protease from Streptomyces parvulus DPUA 1573, the recovery of the protease by aqueous two-phase system and partial biochemical characterization of the enzyme. The aqueous two-phase system was performed according to a 24-full factorial design using polyethylene glycol molar mass, polyethylene glycol concentration, citrate concentration and pH as independent variables. It was analyzed the effect of different ions, surfactants, inhibitors, pH and temperature on enzyme activity. The best conditions for purifying the enzyme were 17.5% polyethylene glycol 8,000, 15% Phosphate and pH 8.0, it was obtained a partition coefficient of 7.33, a yield of 57.49% and a purification factor of 2.10-fold. There was an increase in enzyme activity in the presence of Fe2+ and a decrease in the presence of $\beta$-Mercaptoethanol, phenylmethylsulfonyl fluoride and Iodoacetic acid. The optimum pH was 7.0 and the optimum temperature was 40 ºC. The purified protease exhibited a molecular mass of 41 kDa. The fibrinolytic protease from Streptomyces parvulus proved to be a viable option for the development of a possible drug with fibrinolytic action.

Abstract Solid state fermentation is a promising technology largely used in biotechnology process and is a suitable strategy for producing low-cost enzymatic products. At the present study, a novel enzyme obtained through solid state fermentation using Aspergillus sydowii was herein purified and characterized. The fermentations used coffee ground residue as substrate and the crude enzyme was submitted through further purification steps of: acetonic precipitation, DEAE-Sephadex and Superdex G-75 column. Both crude and purified enzymes were submitted to biochemical characterization of their thermostability, optimal temperature and pH, effects of inhibitors and metal ions. A purified protease was obtained with yield of 5.9-fold and 53% recovery, with maximal proteolytic activity of 352.0 U/mL. SDS-PAGE revealed a band of protein at 47.0 kDa. The enzyme activity was abolished in the presence of phenyl-methyl sulfonyl fluoride and partially inhibited against Triton X-100 (78.0%). The optimal activity was found in pH 8.0 at 45°C of temperature. Besides, the enzyme showed stability between 35°C and 50°C. It was possible to determine appropriate conditions to the obtainment of thermostable proteases with biotechnological interest associated with a method that concomitantly shows excellent production levels and recovery waste raw material in a very profitable process.

Abstract This study aims to evaluate the influence of B. subtilis AP91 spores addition on the mechanical properties of mortars. B. subtilis strain AP91, isolated from rice leaves of the needle variety, which has an early cycle of production, was used at the concentration of 105 spores/mL in mortars with cement-to-sand ratio of 1:3 (by weight) and water-to-cement ratio (w/c) of 0.63. These spores were added in two different ways: in the mixing water and by immersion in a solution containing bacterial spores. Scanning Electron Microscope (SEM) analysis showed crystals with calcium peaks on the EDS, which possibly indicates the presence of bioprecipitated calcium carbonate. The results obtained in the mechanical analysis showed that the bioprecipitation of CaCO3 by B. subtilis strain AP91 was satisfactory, particularly when the spores were added in the mixing water, increasing the compressive strength up to 31%. Thus, it was concluded that the addition of B. subtilis AP91 spores in the mixing water of cement mortars induced biocementation, which increased the compressive strength. This bioprecipitation of calcium carbonate may very well have other advantageous consequences, such as the closure of pores and cracks in cementitious materials that could improve durability properties, although more research is still needed on this matter.

Abstract Copaiba oil is a natural product used by Amazonian populations and recognized for its medicinal properties because it has significant antimicrobial activity for several pathogenic microorganisms. The present work aimed to evaluate and characterize the effect of natural oil produced by copaiba – Copaifera multijuga against multiresistant isolates of bubaline mastitis. The nitrocefin test was performed with isolates of Staphylococcus aureus from bubaline mastitis, which were 100% positive for beta-lactamase enzyme detection. Minimum Bactericidal Concentration (MBC) of 25% to 3.12% was obtained for Enterococcus faecalis and Escherichia coli and 50% and 25% for S. aureus, but Klebsiella pneumoniae and Bacillus subtilis were resistant. MBC with 12.5% and 6.25% oil were obtained for most multiresistant bubaline mastitis isolates from the states of Pernambuco, Ceará, Bahia and Alagoas. The results demonstrated the great potential of using copaiba natural oil in the treatment of buffalo mastitis.

Abstract The industrial demand for proteolytic enzymes is stimulating the search for new enzyme sources. Fungal enzymes are preferred over bacterial enzymes, and more effective and easier to extract. The aim of this work was to evaluate the potential of protease production by solid state fermentation (SSF) of Mucor subtilissimus UCP 1262, evaluate different specific activities, purify and partially characterize the enzyme in terms of biochemical as to the optimal pH and temperature. Initially, the enzyme crude extract was screened for 3 different proteolytic activities, collagenolytic (161.4 U/mL), keratinolytic (39.6 U/mL) and fibrinolytic (26.1 U/mL) in addition to conventional proteinase activity. After ammonium sulfate precipitation, the active fractions with fibrinolytic activity were dialyzed in 15 mM Tris-HCl buffer, pH 8, loaded onto DEAE-Sephadex A50 ion-exchange column and gel filtrated through Superdex 75 HR10/300. The enzyme showed a fibrinolytic maximum activity at 40 C and pH 9,0. The purified enzyme showed activity against a chromogenic chymotrypsin substrate, SDS-PAGE showing a molecular mass of approximately 70 kDa and, the specific activity of 25.93 U/mg. These characteristics suggest that the enzyme could be and efficiently produced in a simple and low-cost way using Mucor subtilissimus UCP 1262 in SSF.

Antimicrobial peptides are considered promising alternatives to antibiotics. Here the authors developed a computational algorithm that starts with peptides naturally occurring in plants and optimizes this starting material to yield new variants which are highly distinct from the parent peptide.

Abstract ApoE3 is the major chylomicron apolipoprotein, binding in a specific liver peripheral cell receptor, allowing transport and normal catabolism of triglyceride-rich lipoprotein constituents. Point mutations in ApoE3 have been associated with Alzheimer’s disease, type III hyperlipoproteinemia, atherosclerosis, telomere shortening and impaired cognitive function. Here, we evaluate the impact of missense SNPs in APOE retrieved from dbSNP through 16 computational prediction tools, and further evaluate the structural impact of convergent deleterious changes using 100 ns molecular dynamics simulations. We have found structural changes in four analyzed variants (Pro102Arg, Arg132Ser, Arg176Cys and Trp294Cys), two of them (Pro102Arg and Arg176Cys) being previously associated with human diseases. In all cases, except for Trp294Cys, there was a loss in the number of hydrogen bonds between CT and NT domains that could result in their detachment. In conclusion, data presented here could increase the knowledge of ApoE3 activity and be a starting point for the study of the impact of variations on APOE gene.

Abstract This work aimed to evaluate the effects of CasuL on growth and viability of 15 mastitis isolates from cows and goats, to determine the synergistic potential between CasuL and antibiotics, and to investigate the effects on bacterial ultrastructure and antibiofilm activity. The lectin inhibited the growth of Staphylococcus isolates from either bovine (Ssp6PD and Sa) or caprine (Ssp5D and Ssp01) mastitis. The minimal inhibitory concentrations were ranged from 3.75 to 15 µg/ml. Synergistic effect was observed for CasuL‐tetracycline against Sa and Ssp6PD and CasuL‐ampicillin against Ssp01. No structural damage was observed under the scanning electron microscope in CasuL treatments. Flow cytometry analysis using thiazol orange and propidium iodide demonstrated that CasuL was unable to reduce the cell viability of the isolates tested. At sub‐inhibitory concentrations, CasuL reduced biofilm formation by the isolates Sa and Ssp5D. However, CasuL‐tetracycline and CasuL‐ampicillin combinations inhibited biofilm formation by Ssp6PD and Ssp01, respectively. In conclusion, CasuL is a bacteriostatic and antibiofilm agent against some mastitis isolates and displayed a synergistic potential when used in combination with either ampicillin (against one isolate) or tetracycline (against two isolates). The results stimulate the evaluation of CasuL for the treatment of mastitis, particularly when used in conjunction with antibiotics.

The fragmentation of quasi-projectiles from the nuclear reaction 40Ca+12C at 25 MeV per nucleon bombarding energy was used to produce α-emission sources. From a careful selection of these sources provided by a complete detection and from comparisons with models of sequential and simultaneous decays, evidence in favor of α-particle clustering from excited 16O, 20Ne and 24Mg is reported. Keywords: Heavy ion reactions, alpha-particle clustering, alpha-conjugate nuclei, Cluster models

Physical exercise stimulates organs, mainly the skeletal muscle, to release a broad range of molecules, recently dubbed exerkines. Among them, RNAs, such as miRNAs, piRNAs, and tRNAs loaded in extracellular vesicles (EVs) have the potential to play a significant role in the way muscle and other organs communicate to translate exercise into health. Low, moderate and high intensity treadmill protocols were applied to rat groups, aiming to investigate the impact of exercise on serum EVs and their associated small RNA molecules. Transmission electron microscopy, resistive pulse sensing, and western blotting were used to investigate EVs morphology, size distribution, concentration and EVs marker proteins. Small RNA libraries from EVs RNA were sequenced. Exercise did not change EVs size, while increased EVs concentration. Twelve miRNAs were found differentially expressed after exercise: rno-miR-128-3p, 103-3p, 330-5p, 148a-3p, 191a-5p, 10b-5p, 93-5p, 25-3p, 142-5p, 3068-3p, 142-3p, and 410-3p. No piRNA was found differentially expressed, and one tRNA, trna8336, was found down-regulated after exercise. The differentially expressed miRNAs were predicted to target genes involved in the MAPK pathway. A single bout of exercise impacts EVs and their small RNA load, reinforcing the need for a more detailed investigation into EVs and their load as mediators of health-promoting exercise.

Continuous monitoring of the tissue temperature surrounding implantable devices could be of great advantage. The degree and duration of the immune activation in response to the implant, which is responsible for signal deterioration, could be inferred from the associated temperature raise and the heating caused by electrical or optogenetical stimulation could be accurately controlled. Within this work, a thin-film platinum RTD embedded in polyimide and a readout system based on the Wheatstone bridge configuration are presented. The RTD offers a sensitivity of 8.5 Ω· °C−1 and a precision of 4.1 Ω. The accuracy of the complete system calibrated for temperatures ranging from 34 to 41 °C lies between the classes A and B defined by the standard IEC 751, which correspond to tolerances of ±0.22 and ±0.48 °C at 37 °C, respectively.

Background: Streptomyces sp. DPUA 1576 from Amazon lichens was studied to protease and fibrinolytic production. A 22 factorial experimental design was applied to optimize its protease enzyme production using two independent variables, namely soybean flour and glucose concentrations. Results: The optimal conditions to obtain high protease production (83.42 U/mL) were 1.26% soybean flour and 1.23% glucose concentration. A polynomial model was fitted to correlate the relationship between the two variables and protease activity. In relation to fibrinolytic activity, the highest activity of 706.5 mm2 was obtained at 1.7% soybean flour and 1.0% glucose concentration, which was 33% higher than plasmin. Fibrinolytic production was not optimized in the studied conditions. Conclusions: These results show that the optimization of the culture medium can enhance protease production, thus becoming a good process for further research. In addition, Streptomyces sp. DPUA 1576, isolated from Amazon lichens, might be a potential strain for fibrinolytic protease production.

This paper presents the quantification, antioxidant and antimicrobial activity of capsaicin, dihydrocapsaicin and the flavonoid chrysoeriol isolated from different extracts (hexane and acetonitrile extracts from whole fruit, peel and seed) of Capsicum frutescens (pimenta malagueta). The acetonitrile extract of the seeds, peel and whole fruits contained capsaicin as a major component, followed in abundance by dihydrocapsaicin and chrysoeriol. The antimicrobial activity of the isolated compounds against seven microorganisms showed chrysoeriol was the most active compound. In the antioxidant test, the acetonitrile extract from the whole fruit showed the highest activity. The antioxidant activity of pimenta malagueta may be correlated with its phenolic content, principally with the most active compound, capsaicin.

OBJECTIVE: The aim of this study was to measure dynamic lung hyperinflation and its influence on dyspnea perception in moderate and severe chronic obstructive pulmonary disease patients after performing activities of daily living. METHODS: We measured inspiratory capacity, sensation of dyspnea, peripheral oxygen saturation, heart rate and respiratory rate in 19 chronic obstructive pulmonary disease patients. These measurements were taken at rest and after performing activities of daily living (e.g., going up and down a set of stairs, going up and down a ramp and sweeping and mopping a room). RESULT: The inspiratory capacity of patients at rest was significantly decreased compared to the capacity of patients after performing activities. The change in inspiratory capacity was -0.67 L after going up and down a ramp, -0.46 L after sweeping and mopping a room, and -0.55 L after climbing up and down a set of stairs. Dyspnea perception increased significantly between rest, sweeping and mopping, and going up and down a set of stairs. Dyspnea perception correlated positively with inspiratory capacity variation (r = 0.85) and respiratory rate (r = 0.37) and negatively with peripheral oxygen saturation (r = -0.28). CONCLUSION: Chronic obstructive pulmonary disease patients exhibited reductions in inspiratory capacity and increases in dyspnea perception during commonly performed activities of daily living, which may limit physical performance in these patients.

OBJECTIVE: To identify clinical and immunological markers associated with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). METHOD: 237 HTLV-I infected individuals were clinically assessed. They were classified according to the Expanded Disability Status Scale (EDSS) and Osame’s Motor Disability Score (OMDS). Cytokine levels were determined in HTLV-I seropositive individuals. RESULTS: 37 patients had HAM/TSP. There was a correlation between the degrees of disability assessed by both scales. There was also a correlation between the duration of HAM/TSP and the severity of disability assessed by either EDSS or OMDS. Higher levels of IFN-gamma were detected in unstimulated peripheral blood mononuclear cells (PBMC) from HAM/TSP patients as compared with HTLV-I carriers. CONCLUSION: This study shows the validity of the neurological scales to classify the degree of neurological disability in HTLV-I carriers and suggests a progressive behavior of HAM/TSP. This study also shows that IFN-gamma in PBMC supernatants are markers of HAM/TSP.OBJETIVO: Identificar marcadores clínicos e imunológicos associados com a mielopatia associada ao HTLV-I/paraparesia espástica tropical (MAH/PET). MÉTODO: 237 indivíduos infectados pelo HTLV-I foram clinicamente avaliados. Eles foram classificados de acordo com a escala expandida do estado de incapacidade de Kurtzke (EDSS) e escala de incapacidade motora de Osame (OMDS). Níveis de citocinas foram determinados nos indivíduos. RESULTADOS: 37 pacientes tinham MAH/PET. Houve correlação entre os graus de incapacidade pelas escalas. Houve também correlação entre a duração da MAH/PET e o grau da incapacidade pelas escalas. Níveis elevados de IFN-gama foram detectados em células mononucleares de sangue periférico (CMSP) não estimuladas de pacientes com MAH/PET quando comparados com indivíduos HTLV-I positivos assintomáticos. CONCLUSÃO: Os dados demonstram a validade das escalas neurológicas para classificar o grau de incapacidade neurológica em portadores do HTLV-I e sugerem o comportamento progressivo da MAH/PET. Este estudo também demonstra que os níveis de IFN-gama em sobrenadante de CMSP são marcadores da MAH/PET.

A study of the structure of the plankton community along the coastal zone of the Casa Caiada-Rio Doce area (Pernambuco, Brazil) is presented. The results obtained indicated that in the protected zones the water presented high turbidity, high temperature, low salinity and high nutrient and oxygen rates. All of these conditions were responsible for the reduction in plankton diversity and an increase in the biomass of the most opportunistic (r-strategist) species e.g. Gyrosigma balticum and Bacillaria paxillifera (Phytoplankton) and Euterpina acutifrons (Zooplankton). The differences found with respect to others area studies performed in pristine conditions indicated that plankton structure could be used as an environmental health indicator and that, in this specific area, it was indicative of a poor quality coastal environment.Foi realizado um estudo sobre a estrutura das comunidades planctônicas ao longo das praias de Casa Caiada e Rio Doce (Pernanbuco, Brasil). A área de estudo sofre grande influência antrópica onde as condições ambientais são controladas pela presença de estruturas costeiras, reduzindo a intensidade da circulação neste ambiente; e pelos efluentes clandestinos de esgoto que aportam águas poluídas para dentro do sistema protegido. Os resultados obtidos indicam que nas zonas protegidas as águas apresentam alta turbidez, temperaturas elevadas, salinidades reduzidas e altas concentrações de nutrientes e oxigênio. Estas condições são responsáveis pela redução da diversidade do plâncton e pelo aumento da biomassa das espécies mais resistentes. As diferenças registradas com respeito a áreas similares, porém não impactadas, parecem indicar que a estrutura planctônica pode ser usada como um indicador da qualidade ambiental, sugerindo uma baixa qualidade das praias em estudo.

A estrongiloidíase é uma das mais importantes helmintíases em países tropicais e estudos epidemiológicos têm demonstrado associação desta parasitose com o vírus HTLV-1. Em regiões onde estes dois agentes são endêmicos a coinfecção pode resultar no desenvolvimento de formas disseminadas da estrongiloidíase assim como em estrongiloidíase recorrente. Enquanto que o vírus HTLV-1 está relacionado com uma alta produção de IFN-γ e desvio da resposta imune para o tipo Th1, a proteção contra helmintos está associada a uma resposta Th2. Devido a este viés da resposta imune, indivíduos infectados pelo HTLV-1 apresentam redução na produção de IL-4, IL-5, IL-13 e IgE, componentes participantes dos mecanismos de defesa contra S. stercoralis. Estas anormalidades constituem a base para a ocorrência de maior freqüência e de formas mais graves da estrongiloidíase em pacientes infectados pelo HTLV-1.

Data generated by environmental research in Antarctica are essential in evaluating how its biodiversity and environment are affected by global-scale changes triggered by ever-increasing human activities. In this work, we describe BrAntIS, the Brazilian Information System on Antarctic Environmental Research, which enables the acquiring, storing, and querying of research data generated by the Brazilian National Institute for Science and Technology on Antarctic Environmental Research. BrAntIS' data model reflects data acquisition and analysis conducted by scientists and organized around field expeditions. We describe future functionalities, such as the use of linked data techniques and support for scientific workflows.

Keratitis treatment has become more complicated due to the emergence of bacterial or fungal pathogens with enhanced antibiotic resistance. The pharmaceutical applications of N-heterocyclic carbene complexes have received remarkable attention due to their antimicrobial properties. In this paper, the new precursor, 3,3'-(p-phenylenedimethylene) bis{1-(2- methyl-allyl)imidazolium} bromide (1a) and its analogous PF6 salt (1b) were synthesized. Furthermore, silver(I) and gold(I) -N-heterocyclic carbene (NHC) complexes [Ag2LBr2/Au2LBr2; 2a/3a], [(Ag2L2)(PF6)2/(Au2L2)(PF6)2; 2b/3b] were developed from their corresponding ligands. All compounds were screened for their antimicrobial activities against multiple keratitis-associated human eye pathogens, including bacteria and fungi. Complexes 2a and 3a showed highest activity, and the effectiveness of 3a was also studied, focusing eradication of pathogen biofilm. Furthermore, the structures of 1a, 2a and 3b were determined using single crystal X-ray analysis, 2b and 3a were optimized theoretically. The mechanism of action of 3a was evaluated by scanning electron microscopy and docking experiments, suggesting that its target is the cell membrane. In summary, 3a may be helpful in developing antimicrobial therapies in patients suffering from keratitis-associated eye infections caused by multidrug-resistant pathogens.

ObjectivesTo measure the oxygen and ventilatory output across all COPD stages performing 18 common ADL and identify the activities that present the highest metabolic and ventilatory output as well as to compare the energy expenditure within each disease severity.Materials and methodsMetabolic (VO2 and VCO2), ventilatory (f and VE), cardiovascular (HR) and dyspnea (Borg score) variables were assessed in one hundred COPD patients during the completion of eighteen ADL grouped into four activities domains: rest, personal care, labor activities and efforts.ResultsThe activities with the highest proportional metabolic and ventilatory output (VO2/VO2max and VE/MVV) were walking with 2.5 Kg in each hand and walking with 5.0 Kg in one hand. Very severe patients presented the highest metabolic, ventilatory output and dyspnea than mild patients (pConclusionsCOPD patients present an increased proportion of energy expenditure while performing activities of daily living. The activities that developed the highest metabolic and ventilatory output are the ones associated to upper and lower limbs movements combined. Very severe patients present the highest proportional estimated metabolic and ventilatory output and dyspnea. Activities of daily living are mainly limited by COPD's reduced ventilatory reserve.

For almost four decades, antimicrobial peptides have been studied, and new classes are being discovered. However, for therapeutic use of these molecules, issues related to the mechanism of action must be answered. In this work, the antimicrobial activity of the hairpinin MBP-1 was studied by the synthesis of two variants, one replacing cysteines and one tryptophan with alanine. Antibacterial activity was abolished in both variants. No membrane disturbance, even in concentrations higher than those required to inhibit the bacteria, was observed in SEM microscopy. The gel retardation assay showed that MBP-1 possesses a higher DNA-binding ability than variants. Finally, molecular modelling showed that the lack of cysteines resulted in structure destabilization and lack of tryptophan resulted in a less flexible peptide, with less solvent assessable surface area, both characteristics that could contribute to absence of activity. In summary, the data here reported add more information about the multiple mechanisms of action of α-hairpinins.

Healthcare-associated infections (HAIs) are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO) is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO) was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3) were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms.