Investigation of the Potential Targets behind the Promising and Highly Selective Antileishmanial Action of Synthetic Flavonoid Derivatives.

Leishmaniases are among the neglected tropical diseases that still cause devastating health, social, and economic consequences to more than 350 million people worldwide. Despite efforts to combat these vector-borne diseases, their incidence does not decrease. Meanwhile, current antileishmanial drugs are old and highly toxic, and safer presentations are unaffordable to the most severely affected human populations. In a previous study by our research group, we synthesized 17 flavonoid derivatives that demonstrated impressive inhibition capacity against rCPB2.8, rCPB3, and rH84Y. These cysteine proteases are highly expressed in the amastigote stage, the target form of the parasite. However, although these compounds have been already described in the literature, until now, the amastigote effect of any of these molecules has not been proven. In this work, we aimed to deeply analyze the antileishmanial action of this set of synthetic flavonoid derivatives by correlating their ability to inhibit cysteine proteases with the action against the parasite. Among all the synthesized flavonoid derivatives, 11 of them showed high activity against amastigotes of Leishmania amazonensis, also providing safety to mammalian host cells. Furthermore, the high production of nitric oxide by infected cells treated with the most active cysteine protease B (CPB) inhibitors confirms a potential immunomodulatory response of macrophages. Besides, considering flavonoids as multitarget drugs, we also investigated other potential antileishmanial mechanisms. The most active compounds were selected to investigate another potential biological pathway behind their antileishmanial action using flow cytometry analysis. The results confirmed an oxidative stress after 48 h of treatment. These data represent an important step toward the validation of CPB as an antileishmanial target, as well as aiding in new drug discovery studies based on this protease.

Angiomatosis bacilar y micobacteriosis atípica en paciente con diagnóstico reciente de infección por el virus de la inmunodeficiencia humana / Bacillary Angiomatosis and Atypical Mycobacteriosis in a patient recently diagnosed with Human Immunodeficiency Virus infection

Múltiples infecciones oportunistas pueden manifestarse simultáneamente cuando la inmunosupresión es grave en pacientes infectados por el virus de la inmunodeficiencia humana. Se presenta un caso de coinfección de VIH, Bartonella spp y Mycobacterium kansasii, siendo escasos los reportes a la fecha de dicha asociación y aun más en pacientes que desconocen su condición de VIH

Multiple opportunistic infections can manifest simultaneously when immunosuppression is severe in patients infected with the human immunodeficiency virus. A case of co-infection with HIV, Bartonella spp and Mycobacterium kansasii is presented, with few reports to date of this association and even more so in patients who are unaware of their HIV status.

Efficacy of a spatial repellent for control of Aedes-borne virus transmission: A cluster-randomized trial in Iquitos, Peru.

Over half the world's population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito-human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = -9.11) and 12.4% (95% CI 4.2%, ∞); z = -2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.

Eryngium foetidum L. (Apiaceae): A Literature Review of Traditional Uses, Chemical Composition, and Pharmacological Activities.

Eryngiumfoetidum L. is popularly known as chicória-do-Pará, is native to the Amazon region, and is widely distributed in Northern Brazil. It is considered a versatile species due to its diversified uses in ethnomedicine, gastronomy, and pharmaceutical industry. The objective of this study was to review the literature on the traditional uses, chemical composition, and pharmacological activities of E. foetidum based on information published in national and international scientific articles between the years 2011 and 2021. Literature searches were performed with the combination of the expressions "Eryngium foetidum L.," "chicória-do-Pará," "traditional uses," "ethnobotany," "volatile compounds," and "essential oil." The species is widely used as a flavoring condiment in beans, meat, duck, and fish, and in the preparation of tucupi (cassava sap), showing to have great importance for the Amazonian food culture. In traditional medicine, it has analgesic, antibacterial, antiflu, and antipyretic applications. The chemical profile is characterized by the presence of aromatic and aliphatic aldehydes, mainly (2E)-2-dodecenal in leaves and 2,3,4-trimethylbenzaldehyde in roots, in addition to fixed compounds such as carotenoids, flavonoids, and phenols. These compounds have shown diverse biological activities and potential antibacterial, anthelmintic, and antioxidant applications, confirming their potential for use in folk medicine. Therefore, it is inferred that this aromatic plant has vast potential uses and is an important alternative as a natural resource for the food and pharmaceutical industries in view of its antioxidant capacity and bioactive compounds.

Survey of beef bulls in Brazil to assess their role as source of infectious agents related to cow infertility.

Poor reproductive performance in beef cattle caused by infectious agents results in major financial losses as a result of reduced pregnancy rates and extended calving intervals. Bulls can be subclinical chronic carriers of bacterial and protozoal agents involved in cow infertility, such as Campylobacter fetus subsp. venerealis, Ureaplasma diversum, Mycoplasma bovigenitalium, Mycoplasma bovis, and Tritrichomonas foetus. Bulls harbor these microorganisms in their preputial crypts and transmit the agents to cows during natural mating. To obtain an overview of the etiologic agents in the preputial mucus of bulls, we aimed to identify, by PCR assay, C. fetus subsp. venerealis, M. bovis, U. diversum, M. bovigenitalium, and T. foetus in Brazilian bulls from farms with high infertility rates. We collected preputial mucus from 210 bulls on 18 beef cattle farms in Brazil between 2019 and 2020. We found at least one of the infectious agents that we were studying in bulls on 16 of the 18 beef cattle farms tested. We detected at least one infectious agent from 159 of 210 (76%) bulls tested, namely C. fetus subsp. venerealis, M. bovis, U. diversum, M. bovigenitalium, and T. foetus in 87 (55%), 84 (53%), 45 (28%), 28 (18%), and 1 (0.6%) animal, respectively. We found 95 bulls (60%) positive for only 1 etiologic agent (single infection) and 64 bulls (40%) carried multiple agents. Our results demonstrate the occurrence of bacterial and protozoal infectious agents that may be related to infertility in Brazilian beef cattle herds.

Aging restricts the ability of mesenchymal stem cells to promote the generation of oligodendrocytes during remyelination.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that leads to severe neurological deficits. Due to their immunomodulatory and neuroprotective activities and their ability to promote the generation of oligodendrocytes, mesenchymal stem cells (MSCs) are currently being developed for autologous cell therapy in MS. As aging reduces the regenerative capacity of all tissues, it is of relevance to investigate whether MSCs retain their pro-oligodendrogenic activity with increasing age. We demonstrate that MSCs derived from aged rats have a reduced capacity to induce oligodendrocyte differentiation of adult CNS stem/progenitor cells. Aging also abolished the ability of MSCs to enhance the generation of myelin-like sheaths in demyelinated cerebellar slice cultures. Finally, in a rat model for CNS demyelination, aging suppressed the capability of systemically transplanted MSCs to boost oligodendrocyte progenitor cell (OPC) differentiation during remyelination. Thus, aging restricts the ability of MSCs to support the generation of oligodendrocytes and consequently inhibits their capacity to enhance the generation of myelin-like sheaths. These findings may impact on the design of therapies using autologous MSCs in older MS patients.

Burden of Influenza in 4 Ecologically Distinct Regions of Peru: Household Active Surveillance of a Community Cohort, 2009-2015.

BACKGROUND: There are limited data on the burden of disease posed by influenza in low- and middle-income countries. Furthermore, most estimates of influenza disease burden worldwide rely on passive sentinel surveillance at health clinics and hospitals that lack accurate population denominators. METHODS: We documented influenza incidence, seasonality, health-system utilization with influenza illness, and vaccination coverage through active community-based surveillance in 4 ecologically distinct regions of Peru over 6 years. Approximately 7200 people in 1500 randomly selected households were visited 3 times per week. Naso- and oropharyngeal swabs were collected from persons with influenza-like illness and tested for influenza virus by real-time reverse-transcription polymerase chain reaction. RESULTS: We followed participants for 35353 person-years (PY). The overall incidence of influenza was 100 per 1000 PY (95% confidence interval [CI], 97-104) and was highest in children aged 2-4 years (256/1000 PY [95% CI, 236-277]). Seasonal incidence trends were similar across sites, with 61% of annual influenza cases occurring during the austral winter (May-September). Of all participants, 44 per 1000 PY (95% CI, 42-46) sought medical care, 0.7 per 1000 PY (95% CI, 0.4-1.0) were hospitalized, and 1 person died (2.8/100000 PY). Influenza vaccine coverage was 27% among children aged 6-23 months and 26% among persons aged ≥65 years. CONCLUSIONS: Our results indicate that 1 in 10 persons develops influenza each year in Peru, with the highest incidence in young children. Active community-based surveillance allows for a better understanding of the true burden and seasonality of disease that is essential to plan the optimal target groups, timing, and cost of national influenza vaccination programs.

Case-Case Analysis Using 7 Years of Travelers' Diarrhea Surveillance Data: Preventive and Travel Medicine Applications in Cusco, Peru.

AbstractIn Cusco, Peru, and South America in general, there is a dearth of travelers' diarrhea (TD) data concerning the clinical features associated with enteropathogen-specific infections and destination-specific risk behaviors. Understanding these factors would allow travel medicine providers to tailor interventions to patients' risk profiles and travel destination. To characterize TD etiology, evaluate region-specific TD risk factors, and examine relationships between preventive recommendations and risk-taking behaviors among medium- to long-term travelers' from high-income countries, we conducted this case-case analysis using 7 years of prospective surveillance data from adult travelers' presenting with TD to a physician in Cusco. At the time of enrollment, participants provided a stool sample and answered survey questions about demographics, risk behaviors, and the clinical features of illness. Stool samples were tested for norovirus (NV), bacteria, and parasites using conventional methods. Data obtained were then analyzed using case-case methods. NV (14%), enterotoxigenic Escherichia coli (11%), and Campylobacter (9%), notably ciprofloxacin-resistant Campylobacter, were the most frequently identified pathogens among adults with TD. Coinfection with multiple enteropathogens occurred in 5% of cases. NV caused severe disease relative to other TD-associated pathogens identified, confining over 90% of infected individuals to bed. Destination-specific risk factors include consumption of the local beverage "chicha," which was associated with Cryptosporidium infection. Preventive interventions, such as vaccines, directed against these pathogens could significantly reduce the burden of TD.

Epidemiology and Genetic Characterization of Noroviruses among Adults in an Endemic Setting, Peruvian Amazon Basin, 2004-2011.

BACKGROUND: Successful vaccination strategies against norovirus will require understanding the burden of disease and relevant genotypes in populations. However, few data are available from cohort studies of adults living in low- and middle-income countries (LMIC). MATERIALS AND METHODS: We conducted a nested case-control study within a Peruvian military cohort to characterize the burden of norovirus infection, predominant genotypes, and associated symptoms from 2004 through 2011. Randomly selected case and control stools were tested for norovirus, bacteria, and parasites. The odds ratio of the association between norovirus infection and diarrhea was estimated using multiple logistic regression and co-infection adjusted attributable fractions were calculated. RESULTS: Of the 3,818 cohort study participants, 624 developed diarrhea. Overall and norovirus-associated diarrhea incidence rates were 42.3 and 6.0 per 100 person-years, respectively. The most prevalent norovirus genogroup was GII (72.5%, 29/40), which was associated with diarrhea (AOR 3.4, 95% CI: 1.3-8.7, P = 0.012). The co-infection adjusted GII attributable fraction was 6.4%. DISCUSSION: Norovirus was a frequent cause of diarrhea in an adult population followed longitudinally in an LMIC setting. Vaccine strategies should consider targeting adults in endemic settings and special populations that could serve as community transmission sources.

Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.

BACKGROUND: A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. METHODS: 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. RESULTS: Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. CONCLUSION: Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D.

Easy access to Evans' oxazolidinones. Stereoselective synthesis and antibacterial activity of a new 2-oxazolidinone derivative.

An interesting new approach was developed for the synthesis of Evans' chiral auxiliaries with excellent yields. In turn, another new stereoselective and efficient strategy has also allowed for the preparation of a 2-oxazolidinone derivative in 34% overall yield from the Morita-Baylis-Hillman adduct. The antibacterial activity of this oxazolidinone was tested against Staphylococcus aureus strains isolated from animals with mastitis infections.

Short-term nutritional counseling reduces body mass index, waist circumference, triceps skinfold and triglycerides in women with metabolic syndrome.

BACKGROUND: It is recognized that the growing epidemic of metabolic syndrome is related to dietary and lifestyle changes. OBJECTIVE: The purpose of this study was to evaluate short-term application of nutritional counseling in women with metabolic syndrome. METHODS: This follow-up study was conducted from September to November 2008 with thirty three women > or =35 years old screened clinically for nutritional counseling. Dietary intake was reported, and biochemical and body composition measures were taken at baseline and after three months of follow-up. RESULTS: Of the 33 women evaluated, 29 patients completed the study. The prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity was high at 38%, 72.4%, 55.2%, and 75.8%, respectively. At the end of three-months of follow-up, a significant decline in body mass index, waist circumference, triceps skinfold, and triglycerides was observed, as was an increase in calcium and vitamin D intake. The multiple regression analysis showed that changes in body mass index, triceps skinfold, waist circumference and triglyceride levels after nutritional intervention were positively associated with changes in anthropometric (loss of body weight) and biochemical (decrease of TG/HDL-c ratio) parameters. Moreover, waist circumference changes were negatively associated with changes in calcium and vitamin D intake. CONCLUSION: Short-term nutritional counseling improved some factors of metabolic syndrome. Moreover, the increases in calcium and vitamin D consumption can be associated with the improvement in markers of metabolic syndrome.

Climate and acute/subacute paracoccidioidomycosis in a hyper-endemic area in Brazil.

BACKGROUND: Paracoccidioidomycosis (PCM) is Latin America's most prevalent systemic mycosis, carrying an important social burden. Its agent, Paracoccidioides brasiliensis, has rarely been identified in nature. Studies characterizing acute/subacute PCM incidence and their relationship with climate variables are not available. This work analysed a series of acute/subacute cases that occurred in the Botucatu area, São Paulo State, Brazil, from 1969 to 1999, as an outcome of weather variability. METHODS: Stepwise regression of annual data was applied to model incidence, calculated based on 91 cases, from lagged variables: antecedent precipitation, air temperature, soil water storage, absolute and relative air humidity, and Southern Oscillation Index (SOI). RESULTS: Multiple regression analyses resulted in a model, which explains 49% of the incidence variance, taking into account the absolute air humidity in the year of exposure, soil water storage and SOI of the previous 2 years. CONCLUSIONS: The correlations may reflect enhanced fungal growth after increase in soil water storage in the longer term and greater spore release with increase in absolute air humidity in the short term.

Co-composting of poultry manure with low quantities of carbon-rich materials.

To study the feasibility of co-composting poultry manure with low quantities of high-value, carbon-rich materials experiments to characterize three pilot-scale piles were carried out. The piles comprised poultry manure (pile 1), poultry manure and straw (pile 2) and poultry manure and sawdust (pile 3), using wood chips as bulking agent. Pile 1 presented the highest losses of organic matter and nitrogen contents (> or = 92.9% and 92.0%, respectively). Although a thermophilic phase (temperature > 40 degrees C) was not verified for this pile, the final compost was stable (class IV) and free of pathogen indicator micro-organisms but it was the most phytotoxic, and presented a humic and fulvic acids ratio (HA/FA) that was less than 1. In contrast, piles 2 and 3 sustained thermophilic phases and produced stable (class V) and mature (HA/FA > 1) composts. Pile 2 showed the lowest loss in nitrogen content (88.9%) and produced the final compost with the highest C/N ratio (14.7) and the lowest value of electrical conductivity (3.9 mS cm(-1)). This study showed that it is possible to reduce the costs of poultry manure composting, namely the costs associated with the use of carbon-rich materials, given that the final co-composts presented parameters within the range of those recommended by the Second Draft Proposal for compost quality.

Diversity of bacterial isolates from commercial and homemade composts.

The diversity of heterotrophic bacterial isolates of three commercial and two homemade composts was studied. The commercial composts were produced from poultry litter (PC), sewage sludge (SC), municipal solid waste (MC), and homemade composts (thermal compost [DC] and vermicompost [VC]) from food wastes. The taxonomic and physiological diversity of the heterotrophic culturable bacteria was assessed using phenotypic and genotypic characterization and the analysis of the partial 16S rRNA gene sequence. Composts DC and SC presented the higher genotypic diversity, as could be inferred from the number of distinct genotypic patterns observed, 28 and 21, respectively. Gram-positive bacteria, mainly Firmicutes, were predominant in all the composts. Some organisms related with taxa rarely reported in composts, as Rhodanobacter spathiphylli, Moraxella osloensis, Lysobacter, Corynebacterium, Pigmentiphaga kullae, and new taxa were also isolated. The highest relative proportion of isolates able to degrade starch was found in compost SC (> 70%), to degrade gelatine in compost DC (> 70%), to degrade Tween 80 in compost PC (> 90%), and to degrade poly-epsilon-caprolactones in compost DC (> 80%). Compost MC presented the lowest relative proportions of isolates able to degrade starch (< 25%), gelatine (< 20%), and poly-epsilon-caprolactone (< 40%). When compared with the others, the homemade composts presented higher relative proportions of Gram-positive isolates able to inhibit the target organisms Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, or Pseudomonas aeruginosa. In compost MC, none of the Gram-positive isolates was able to inhibit those targets.

Efectividad de la técnica de relajación de schultz modificada en la parte final de la clase de educación física / Effectiveness of the modified Schultz relaxation technique in the final part of the physical education class

Se realizó un estudio experimental prospectivo con el objetivo de evaluar la eficacia de la Técnica de Relajación de Schultz modificada, para la recuperación de los estudiantes en la parte final de la clase de Educación Física. Se seleccionaron de forma aleatoria dos grupos de 32 estudiantes del sexo femenino de la carrera de Medicina; un grupo recibió la técnica de relajación de Schultz modificada y el otro recibió la técnica de relajación tradicional. El estudio se llevó a cabo en el segundo semestre del curso 2003–2004, se tomó el pulso y la frecuencia respiratoria en la parte final de las tres partes en que se divide la clase. Los resultados obtenidos en la misma demostraron que la recuperación con la técnica de relajación de Schultz modificada en los estudiantes del grupo experimental fue superior a los estudiantes del grupo de control en un 28 por ciento

Efectividad de la técnica de relajación de schultz modificada en la parte final de la clase de educación física / Effectiveness of the modified Schultz relaxation technique in the final part of the physical education class

Se realizó un estudio experimental prospectivo con el objetivo de evaluar la eficacia de la Técnica de Relajación de Schultz modificada, para la recuperación de los estudiantes en la parte final de la clase de Educación Física. Se seleccionaron de forma aleatoria dos grupos de 32 estudiantes del sexo femenino de la carrera de Medicina; un grupo recibió la técnica de relajación de Schultz modificada y el otro recibió la técnica de relajación tradicional. El estudio se llevó a cabo en el segundo semestre del curso 2003–2004, se tomó el pulso y la frecuencia respiratoria en la parte final de las tres partes en que se divide la clase. Los resultados obtenidos en la misma demostraron que la recuperación con la técnica de relajación de Schultz modificada en los estudiantes del grupo experimental fue superior a los estudiantes del grupo de control en un 28 por ciento(AU)

Nasopharyngeal colonization by Haemophilus influenzae in children attending day-care centers, in Ribeirão Preto, State of São Paulo, Brazil

A colonização da nasofaringe por Haemophilus influenzae (Hi) foi estudada em 114 crianças saudáveis com menos de 3 anos de idade e que freqüentam creches (day-care centers DCC) em Ribeirão Preto, estado de São Paulo, Brasil. Para cada uma das cepas isoladas foram determinados o biótipo, o sorotipo (por antisoro especifico e PCR) e a sensibilidade a 14 antibióticos. A freqüência de colonização por Hi foi de 72,0 por cento. As cepas isoladas foram identificadas como pertencentes aos biótipos II (36,5 po cento), I (21,5 por cento), V (18,2 por cento) e III (16,1 por cento). A freqüência encontrada de cepas encapsuladas foi de 3,2 por cento para o tipo f, 1,0 por cento para o tipo b, 1,0 por cento para o tipo d e 1,0 por cento para o tipo e. A resistência para trimetoprim-sulfametoxazole e ampicilina foi de 46,2 por cento e 10,7 por cento respectivamente. Resistência múltipla foi encontrada em 14 (15,0 por cento) das cepas analisadas. 13,9 por cento das cepas analisadas eram produtoras de b-lactamase, e não foi recuperada nenhuma cepa b-lactamase negativa e ampicilina resistente. DCCs são considerados locais de risco, com um alto potencial de disseminação de microrganismos e por isto devem ser continuadamente monitorados com a finalidade de detectar a eliminação da colonização da nasofaringe por cepas H. influenzae tipo b das crianças que freqüentam DCC, ou detectar a sua substituição por outro tipo de cepa.

Comparison of two slide agglutination serotyping methods and PCR-based capsule typing for the characterization of Haemophilus influenzae serotypes

Noventa e três isolados nasofaringeanos de H. influenzae foram sorotipados através de 2 métodos de aglutinação em lamina (SAST 1 e SAST 2) e os resultados foram comparados com a sorotipagem por PCR. SAST 1 apresentou uma baixa correlação com os resultados obtidos por PCR (75,2 por cento) enquanto que SAST 2 mostrou uma melhor concordância com os resultados da técnica molecular (93,5 por cento). Estes resultados indicam que SAST 2 pode ser um método alternativo para a correta detecção de H. influenzae tipo b.