Intramacrophage lipid accumulation compromises T cell responses and is associated with impaired drug therapy against visceral leishmaniasis.

Under perturbing conditions such as infection with Leishmania, a protozoan parasite living within the phagosomes in mammalian macrophages, cellular and organellar structures, and metabolism are dynamically regulated for neutralizing the pressure of parasitism. However, how modulations of the host cell metabolic pathways support Leishmania infection remains unknown. Herein, we report that lipid accumulation heightens the susceptibility of mice to L. donovani infection and promotes resistance to first-line anti-leishmanial drugs. Despite being pro-inflammatory, the in vitro generated uninfected lipid-laden macrophages (LLMs) or adipose-tissue macrophages (ATMs) display lower levels of reactive oxygen and nitrogen species. Upon infection, LLMs secrete higher IL-10 and lower IL-12p70 cytokines, inhibiting CD4+ T cell activation and Th1 response suggesting a key modulatory role for intramacrophage lipid accumulation in anti-leishmanial host defence. We, therefore, examined this causal relationship between lipids and immunomodulation using an in vivo high-fat diet (HFD) mouse model. HFD increased the susceptibility to L. donovani infection accompanied by a defective CD4+ Th1 and CD8+ T cell response. The white adipose tissue of HFD mice displays increased susceptibility to L. donovani infection with the preferential infection of F4/80+ CD11b+ CD11c+ macrophages with higher levels of neutral lipids reserve. The HFD increased resistance to a first-line anti-leishmanial drug associated with a defective adaptive immune response. These data demonstrate that the accumulation of neutral lipids contributes to susceptibility to visceral leishmaniasis hindering host-protective immune response and reducing the efficacy of antiparasitic drug therapies.

Epidemic thresholds and human mobility.

A comprehensive view of disease epidemics demands a deep understanding of the complex interplay between human behaviour and infectious diseases. Here, we propose a flexible modelling framework that brings conclusions about the influence of human mobility and disease transmission on early epidemic growth, with applicability in outbreak preparedness. We use random matrix theory to compute an epidemic threshold, equivalent to the basic reproduction number [Formula: see text], for a SIR metapopulation model. The model includes both systematic and random features of human mobility. Variations in disease transmission rates, mobility modes (i.e. commuting and migration), and connectivity strengths determine the threshold value and whether or not a disease may potentially establish in the population, as well as the local incidence distribution.

Leishmania donovani Induces Multiple Dynamic Responses in the Metabolome Associated with Amastigote Differentiation and Maturation Inside the Human Macrophage.

Leishmania donovani infection of macrophages drives profound changes in the metabolism of both the host macrophage and the parasite, which undergoes different phases of development culminating in replication and propagation. However, the dynamics of this parasite-macrophage cometabolome are poorly understood. In this study, a multiplatform metabolomics pipeline combining untargeted, high-resolution CE-TOF/MS and LC-QTOF/MS with targeted LC-QqQ/MS was followed to characterize the metabolome alterations induced in L. donovani-infected human monocyte-derived macrophages from different donors at 12, 36, and 72 h post-infection. The set of alterations known to occur during Leishmania infection of macrophages, substantially expanded in this investigation, characterized the dynamics of the glycerophospholipid, sphingolipid, purine, pentose phosphate, glycolytic, TCA, and amino acid metabolism. Our results showed that only citrulline, arginine, and glutamine exhibited constant trends across all studied infection time points, while most metabolite alterations underwent a partial recovery during amastigote maturation. We determined a major metabolite response pointing to an early induction of sphingomyelinase and phospholipase activities and correlated with amino acid depletion. These data represent a comprehensive overview of the metabolome alterations occurring during promastigote-to-amastigote differentiation and maturation of L. donovani inside macrophages that contributes to our understanding of the relationship between L. donovani pathogenesis and metabolic dysregulation.

Diversity and prevalence of intestinal parasites of zoonotic potential in animal hosts from different biomes in the central region of Brazil.

The Brazilian state of Mato Grosso comprises the biomes Cerrado, Pantanal, and Amazon rainforest. The animals that make up the biodiversity of these biomes have an ongoing relationship with domestic animals. This study aimed to describe the prevalence and diversity of intestinal parasites in different class of animal hosts, domestic and wild, from the three biomes of Brazil's central region, during 2019. We analyzed animal faecal samples by sedimentation tests and centrifugal flotation in sucrose. The Shannon index test to calculate diversity and equitability, was used. In the 280 samples analyzed, 79.64% was positive. Domestic animals showed positivity of 87% and wild animals of 51%, being mammals the most prevalent, with 81%. Blastocystis sp. was the most prevalent protozoan, and Ascaris sp. of the helminths. Shannon's indexes were higher for the Pantanal. Overall, pigs, cows, and chickens had high prevalence values and diversity and equitability of enteroparasites. Due to the great diversity of parasites found in pigs, cows and chickens, these animals can play an important role in the transmission and maintenance of the infection to other mammals, including humans.

Dientes primarios verdes por hiperbilirubinemia / Dentes decíduos verdes por hiperbilirubinemia / Green deciduous teeth due to hyperbilirubinemia

Definida como una concentración sérica de bilirrubina, la hiperbilirrubinemia es una condición rara y puede ser causada por cualquier factor que eleve la carga de bilirrubina a ser metabolizada por el hígado. Así, la bilirrubina se distribuye por los tejidos corporales y se acumula en los tejidos duros, incluso, en los dientes primarios. El objetivo de este trabajo es relatar un caso clínico sobre la repercusión severa de la hiperbilirrubinemia en dientes primarios y sus manifestaciones bucales en la primera infancia, como dientes verdosos. Paciente del sexo masculino, 3 años y 8 meses, estuvo en clínica odontológica para evaluación de "manchas verdes en los dientes". En su historia médica se observó que nació prematuro y tuvo complicaciones posparto que evolucionaron para sepsis Dientes primarios verdes por hiperbilirrubinemiaIvana Aguiar Raposo,1..... Ronilza Matos,2.....• Marta Verônica Souto de Araujo,3..... •Tamara Kerber Tedesko,4.....José Carlos Pettorossi Imparato,5..... Revista de Odontopediatría Latinoamericana¹ São Leopoldo Mandic Campinas, Sao Paulo, Brasil.2 Universidade Paulista. 3 Universidade Federal de Pernambuco.4 Universidade Federal de Santa Maria.5 Universidade São Paulo - USP.Casos ClínicosDOI: 10.47990/alop.v11i2.304y, como consecuencia del uso de varios medicamentos, desarrolló un cuadro de hiperbilirrubinemia. El examen clínico dental constató la presencia de manchas verdes en los 20 dientes primarios, ausencia de lesión de caries, encías sanas y buena condición de higiene bucal. Se concluye que los altos niveles de bilirrubina desarrollados por el niño prematuro asociados a septicemia pueden llevar a la pigmentación verde (coloración intrínseca) en los dientes primarios durante el periodo de calcificación de los mismos (odontogénesis), incluso a la afectación de los dientes permanentes. Por eso, es relevante el conocimiento de la historia médica del niño desde el nacimiento para el establecimiento del diagnóstico y pronóstico de las alteraciones dentales

Defined as a serum bilirubin concentration, hyperbilirubinemia is a rare condition and can be caused by any factor that raises the bilirubin load to be metabolized by the liver. Thus, bilirubin is distributed throughout the body's tissues and accumulates in hard tissues, including primary teeth. The aim of this work is to report a clinical case about the severe repercussion of hyperbilirubinemia in primary teeth, and its early childhood manifestations, such as greenish teeth. A male patient, 3 years and 8 months old, attended the dental clinic for evaluation of "green spots on teeth". Medical history revealed that the child had premature birth and postpartum complications that evolved into sepsis, and due to the use of several drugs, developed hyperbilirubinemia. The dental clinical examination showed the presence of green spots on all 20 deciduous teeth, absence of carious lesions, healthy gums and good oral hygiene conditions. We conclude

Chronic heart diseases as the most prevalent comorbidities among deaths by COVID-19 in Brazil.

Age, sex and presence of comorbidities are risk factors associated with COVID-19. Hypertension, diabetes and heart disease are the most common comorbidities in patients with COVID-19. The objective of this study was to estimate the prevalence of patients with comorbidities who died of COVID-19 in Brazil. Searches of data were carried out on the official pages of the 26 State health departments and the federal district. The random-effect method was used to calculate the prevalence of patients with comorbidities who died. From the beginning of the pandemic in Brazil until May 20, 2020, 276,703 cases of COVID-19 were notified in Brazil, 6.4% died, 58.6% of whom were male. The prevalence of comorbidities among deaths was 83% (95% CI: 79 - 87), with heart disease and diabetes being the most prevalent. To our knowledge, this study represents the first large analysis of cases of patients with confirmed COVID-19 in Brazil. There is a high prevalence of comorbidities (83%) among patients who died from COVID-19 in Brazil, with heart disease being the most prevalent. This is important considering the possible secondary effects produced by drugs such as hydroxychloroquine.

Metaplastic breast carcinoma in a pregnant woman: case report / Carcinoma metaplásico da mama em uma gestante: relato de caso

Breast cancer is the most common malignant neoplasm diagnosed during pregnancy. Metaplastic carcinoma is a rare type of breast cancer, representing 1.5% out of all kinds. This is a case report of metaplastic carcinoma in a pregnant woman aged 39 years

O câncer de mama é a neoplasia maligna mais comumente diagnosticado durante a gestação. O carcinoma metaplásico é um tipo raro de câncer mamário que representa 1,5% de todos os tipos. A seguir, é relatado um caso de carcinoma metaplásico em gestante de 39 anos.

FoxN1-dependent thymic epithelial cells promote T-cell leukemia development.

T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphomas (T-LBL) are aggressive malignancies of thymocytes. The role of thymic microenvironmental cells and stromal factors in thymocyte malignant transformation and T-ALL development remains little explored. Here, using the TEL-JAK2 transgenic (TJ2-Tg) mouse model of T-ALL/LBL, which is driven by constitutive JAK/STAT signaling and characterized by the acquisition of Notch1 mutations, we sought to identify stromal cell alterations associated with thymic leukemogenesis. Immunofluorescence analyses showed that thymic lymphomas presented epithelial areas characterized by keratin (Krt) 5 and Krt8 expression, adjacently to epithelial-free areas negative for Krt expression. Both areas contained abundant laminin (extracellular matrix) and ER-TR7+ (fibroblasts) CD31+ (endothelial) and CD11c+ (dendritic) cells. Besides Krt5, Krt-positive areas harbored medullary thymic epithelial cells (TECs) labeled by Ulex europaeus agglutinin-1. By performing flow cytometry and RNA sequencing analyses of thymic lymphomas, we observed an enrichment in medullary TEC markers in detriment of cortical TEC markers. To assess whether TECs are important for T-ALL/LBL development, we generated TJ2-Tg mice heterozygous for the FoxN1 transcription factor nude null mutation (Foxn1+/nu). Strikingly, in TJ2-Tg;Foxn1+/nu compound mice, both emergence of malignant cells in preleukemic thymi and overt T-ALL onset were significantly delayed. Moreover, in transplantation assays, leukemic cell expansion within the thymus of recipient Foxn1+/nu mice was reduced as compared with control littermates. Since thymopoesis is largely normal in Foxn1+/nu mice, these results indicate that FoxN1 haploinsufficiency in TECs has a more profound impact in thymic leukemogenesis.

Real-Time Telemetry System for Monitoring Motion of Ships Based on Inertial Sensors.

A telemetry system for real-time monitoring of the motions, position, speed and course of a ship at sea is presented in this work. The system, conceived as a subsystem of a radar cross-section measurement unit, could also be used in other applications as ships dynamics characterization, on-board cranes, antenna stabilizers, etc. This system was designed to be stand-alone, reliable, easy to deploy, low-cost and free of requirements related to stabilization procedures. In order to achieve such a unique combination of functionalities, we have developed a telemetry system based on redundant inertial and magnetic sensors and GPS (Global Positioning System) measurements. It provides a proper data storage and also has real-time radio data transmission capabilities to an on-shore station. The output of the system can be used either for on-line or off-line processing. Additionally, the system uses dual technologies and COTS (Commercial Off-The-Shelf) components. Motion-positioning measurements and radio data link tests were successfully carried out in several ships of the Spanish Navy, proving the compliance with the design targets and validating our telemetry system.

Transgenic human embryonic stem cells overexpressing FGF2 stimulate neuroprotection following spinal cord ventral root avulsion.

Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold. The spinal cords were processed to evaluate neuronal survival, synaptic stability, and glial reactivity two weeks post lesion. Then, qRT-PCR was used to assess gene expression of ß2-microglobulin (ß2m), TNFα, IL1ß, IL6 and IL10 in the spinal cord in vivo and FGF2 mRNA levels in hESC in vitro. The results indicate that hESC overexpressing FGF2 significantly rescued avulsed motoneurons, preserving synaptic covering and reducing astroglial reactivity. The cells were also shown to express BDNF and GDNF at the site of injury. Additionally, engraftment of hESC led to a significant reduction in mRNA levels of TNFα at the spinal cord ventral horn, indicating their immunomodulatory properties. Overall, the present data suggest that hESC overexpressing FGF2 are neuroprotective and can shift gene expression towards an anti-inflammatory environment.

Depletion of enteroendocrine and mucus-secreting cells is associated with colorectal carcinogenesis severity and impaired intestinal motility in rats.

This study investigated the relationship between enteroendocrine and mucus-secreting cells distribution, the severity of colonic mucosal injury and intestinal motility in experimental colorectal carcinogenesis. Using a standardized murine model of colorectal carcinogenesis, eight-weeks-old female Wistar rats weighting 147.30 ± 29.15g were randomized into two groups receiving a subcutaneous injection of 0.9% saline (control) or the chemical carcinogen 1,2-dimethylhydrazine (DMH) at 20 mg/kg per week during 10 weeks. Aberrant crypt foci (ACF) were more frequent in DMH group compared to control group (P < 0.001). The number of enteroendocrine and mucus-secreting cells, and intestinal motility was reduced in DMH animals (P < 0.05). The distribution of enteric neurons was similar in both groups. In DMH animals there was a direct correlation between colonic motility and distribution of enteroendocrine (R(2) = 0.68, P < 0.05) and mucus-secreting cells (R(2) = 0.77, P < 0.05). Inverse correlation between the number of ACF, mucus-secreting cells (R(2) = -0.57, P < 0.05), and enteroendocrine cells (R(2) = -0.74, P < 0.05) was also observed. There was inverse correlation between the severity of the mucosal lesion, the number of mucus-secreting cells (R(2) = -0.83, P < 0.05) and enteroendocrine cells (R(2) = -0.96, P < 0.05). There was a direct correlation between nucleolar organizer regions (AgNOR) and ACF number (R(2) = 0.62; P < 0.01). Inverse correlation was also found between AgNOR, the number of mucus-secreting cells (R(2) = -0.76; P < 0.001), and enteroendocrine cells (R(2) = -0.86; P < 0.001). Taken together, the results indicated that colonic malignant transformation is related to depletion of mucus-secreting and enteroendocrine cells, which was a useful indicator of the evolutionary status of intestinal neoplasm, partially explaining the intestinal motility disorders in the early stages of colorectal carcinogenesis.

Acute and chronic observations of complete atrioventricular block in rats.

The mechanisms of production, and gross, microscopic and electrocardiograhic findings of surgically-induced complete heart block (CHB) in the adult rat are presented. This is an effective in vivo model for establishing alternative methods to electronic pacemakers and for providing detailed information aimed at replacement, reduction and refinement of the technique. Sternal thoracotomy was employed to identify the epicardial fat pad by the aortic root, used as a landmark for cauterization of the atrioventricular (AV) node. Stable CHB was produced in 60 rats with a 70% survival rate. The best survival rate was observed in 8-week-old animals weighing 221 ± 27.6 g. Heart rate before cauterization was 387 ± 55 bpm, reduced after cauterization to 126 ± 40 bpm in the survival and to 65 ± 19 bpm in the non-survival groups. At 30 days findings were: elevated left ventricular end-diastolic pressure (21 ± 5.4 mmHg, P < 0.05); maximal rate of rise of left ventricular pressure (LVP) during isovolumetric contraction (2192 ± 235 mmHg/s, P < 0.05); maximal rate of decrease of LVP (-1658 ± 191 mmHg/s, P < 0.05); isovolumetric relaxation constant (5.7 ± 0.8 ms, P < 0.05) with wet-to-dry lung-weight ratio (78.1 ± 0.4, P < 0.05); heart weight/body weight (0.6 ± 0.1, P < 0.05); heart volume (1.8 ± 0.3 mL, P < 0.05); longitudinal diameter (20.2 ± 1.91 mm, P < 0.05); and transversal diameter (17.0 ± 1.4 mm, P < 0.05) with supported dilated cardiomyopathy which culminated in chronic heart failure. CHB hearts had increased preload and replacement of myofibrils by collagen. CHB was achieved reproducibly by cauterization of the rat AV node and/or His bundle. This led to electrophysiological, hemodynamic, and structural remodeling, and could be useful in long-term cardiac remodeling assessments and potential therapy development.

Plantas medicinais no tratamento de doenças respiratórias na infância: uma visão do saber popular / Medicinal plants in the treatment of respiratoty diseases in childhood: a view from popular knowledge

nvestiga o saber popular sobre o uso de plantas medicinais no tratamento de doenças respiratórias na infância. Estudo descritivo exploratório de natureza qualitativa, realizado em Juazeiro do Norte/CE com vinte e duas mães e/ou responsáveis de crianças usuárias da Estratégia Saúde da Família. A coleta de dados foi efetuada entre os meses de junho e julho de 2011 através de entrevista semiestruturada. Empregou-se a técnica do Discurso do Sujeito Coletivo para análise de dados. A pesquisa indicou que o saber popular tem grande significado e é amplamente aceito, sendo utilizado em algumas vezes em substituição aos medicamentos sintéticos. Ressaltou ainda, a relevância da transmissão cultural deste saber por gerações. Acreditamos na importância de que os profissionais da saúde discutam as práticas populares de saúde para que possam atuar de forma mais efetiva na resolução dos reais problemas de saúde, aliando o conhecimento popular ao científico e fortalecendo tais práticas.

Importância da avaliação pré-anestésica: relato de caso de paciente com apneia obstrutiva do sono / Importance of pre-anesthetic evaluation: case report of a patient with obstructive sleep apnea / Importancia de la evaluación preanestésica: relato de caso de paciente con apnea obstructiva del sueño

JUSTIFICATIVA E OBJETIVOS: O objetivo deste relato foi mostrar a importância da avaliação pré-anestésica na redução da morbimortalidade de pacientes cirúrgicos e alertar para os problemas e cuidados anestésicos associados com apneia obstrutiva do sono. RELATO DO CASO: Paciente masculino, 28 anos, obeso classe II, asmático, portador de apneia do sono, hipertenso, encaminhado ao ambulatório de pré-anestésico para avaliação de cirurgia de uvuloplastia sob anestesia geral. Após orientação sobre a apneia obstrutiva do sono, esclarecimento ao paciente quanto os riscos do procedimento e discussão com o cirurgião, optou-se por rever a indicação cirúrgica e adiar o procedimento. CONCLUSÕES: O ambulatório de pré-anestésico é de máxima importância na redução da morbimortalidade do paciente cirúrgico e, principalmente, na avaliação de pacientes com apneia obstrutiva do sono, revelando-se fundamental para a programação anestésico-cirúrgica, orientando condutas a serem tomadas e interferindo positivamente no prognóstico do paciente.

BACKGROUND AND OBJECTIVES: The objective of this report was to show the importance of pre-anesthetic assessment in reducing morbidity and mortality of surgical patients and alert to problems and anesthetic care associated with obstructive sleep apnea. CASE REPORT: This is a 28-year old male patient with class II obesity, sleep apnea, hypertension, referred to the pre-anesthetic outpatient clinic for evaluation of uvuloplasty under general anesthesia. After orientation on sleep apnea, explaining to the patient the risks associated with the procedure, and discussing with the surgeon, we decided to review the surgical indication and postpone the procedure. CONCLUSIONS: The pre-anesthetic outpatient clinic is extremely important in reducing morbidity as well as mortality of surgical patients and, especially, in evaluating patients with obstructive sleep apnea, showing to be fundamental for the anesthetic-surgical schedule, orienting conducts to be followed, and interfering positively on patient prognosis.

JUSTIFICATIVA Y OBJETIVOS: El objetivo de este relato fue mostrar la importancia de la evaluación preanestésica en la reducción de la morbimortalidad de pacientes quirúrgicos y alertar los problemas y cuidados anestésicos asociados con la apnea obstructiva del sueño. RELATO DEL CASO: Paciente masculino, 28 años, obeso, clase II, asmático, portador de apnea del sueño, hipertenso, derivado al ambulatorio de preanestesia para la evaluación de cirugía de uvuloplastia bajo anestesia general. Después de la orientación sobre la apnea obstructiva del sueño, de la aclaración al paciente en cuanto a los riesgos del procedimiento y de la discusión con el cirujano, decidimos analizar nuevamente la indicación quirúrgica y postergar el procedimiento. CONCLUSIONES: El ambulatorio de preanestésico es de máxima importancia para la reducción de la morbimortalidad del paciente quirúrgico y principalmente, para la evaluación de los pacientes con apnea obstructiva del sueño, siendo fundamental para la programación anestésico-quirúrgica, orientando las conductas que serán tomadas e interfiriendo positivamente en el pronóstico del paciente.

Importance of pre-anesthetic evaluation: case report of a patient with obstructive sleep apnea.

BACKGROUND AND OBJECTIVES: The objective of this report was to show the importance of pre-anesthetic assessment in reducing morbidity and mortality of surgical patients and alert to problems and anesthetic care associated with obstructive sleep apnea. CASE REPORT: This is a 28-year old male patient with class II obesity, sleep apnea, hypertension, referred to the pre-anesthetic outpatient clinic for evaluation of uvuloplasty under general anesthesia. After orientation on sleep apnea, explaining to the patient the risks associated with the procedure, and discussing with the surgeon, we decided to review the surgical indication and postpone the procedure. CONCLUSIONS: The pre-anesthetic outpatient clinic is extremely important in reducing morbidity as well as mortality of surgical patients and, especially, in evaluating patients with obstructive sleep apnea, showing to be fundamental for the anesthetic-surgical schedule, orienting conducts to be followed, and interfering positively on patient prognosis.

Method-of-moments formulation for the analysis of plasmonic nano-optical antennas.

We present a surface integral equation (SIE) to model the electromagnetic behavior of metallic objects at optical frequencies. The electric and magnetic current combined field integral equation considering both tangential and normal equations is applied. The SIE is solved by using a method-of-moments (MoM) formulation. The SIE-MoM approach is applied only on the material boundary surfaces and interfaces, avoiding the cumbersome volumetric discretization of the objects and the surrounding space required in differential-equation formulations. Some canonical examples have been analyzed, and the results have been compared with analytical reference solutions in order to prove the accuracy of the proposed method. Finally, two plasmonic Yagi-Uda nanoantennas have been analyzed, illustrating the applicability of the method to the solution of real plasmonic problems.

Controlling product selection in the photodissociation of formaldehyde: direct quantum dynamics from the S1 barrier.

Controlling the selectivity between H(2)+CO and H+HCO in the S(1)/S(0) nonadiabatic photodissociation of formaldehyde has been investigated using direct quantum dynamics. Simulations started from the S(1) transition state have suggested that a key feature for controlling the branching ratio of ground-state products is the size of the momentum given to the wavepacket along the transition vector. Our results show that letting the wavepacket fall down from the barrier to the conical intersection with no initial momentum leads to H(2)+CO, while extra momentum toward products favors the formation of H+HCO through the same conical intersection. Quantum dynamics results are interpreted in semiclassical terms with the aid of a Mulliken-like analysis of the final population distribution among both products and the reactant on each electronic state.