Admission for Imported Malaria in Children, in Two Hospitals of Lisbon Urban Area

Introdução: Apesar de em Portugal não haver malária endógena,a crescente mobilidade das populações e os laços históricos com África possibilitam a importação de casos para o nosso país. O presente estudo pretende contribuir para melhorar o conhecimento epidemiológico e clínico da malária importada na região de Lisboa. Métodos: Realizou-se um estudo descritivo das crianças com malária, internadas em dois hospitais da Grande Lisboa, durante um período de seis anos (1999-2004). Resultados: Foram identificados 134 casos, sendo a mediana das idades de sete anos. A maioria (93,3%) era de origem africana e referia estadia em região endémica (90%). O Plasmodium falciparum foi o agente etiológico mais frequente (73%). A febre foi a manifestação clínica mais frequente, seguida de manifestações gastrointestinais e cefaleias. Ocorreram complicações em 42% dos doentes, sendo a trombocitopenia (19,4%) e a anemia grave (9%) as mais frequentes. A halofantrina e o quinino foram os anti-maláricos mais usados. Conclusões: A malária importada é uma patologia relativamente comum na Grande Lisboa e, dada a inespecificidade do quadro clínico, todas as crianças febris ou doentes com estadia recente num país endémico devem ser rastreadas para esta entidade

Snoring in Portuguese primary school children

OBJECTIVE: To determine the prevalence of snoring and its potential associations with sleep problems, such as daytime symptoms, medical conditions, school performance, and behavioral disturbances in Portuguese children attending primary school. METHODS: A previously validated questionnaire was sent to the parents of 1381 children attending primary schools in a parish of Coimbra, Portugal. To assess behavioral disturbances, the Portuguese version of Rutter's Children's Behavior Questionnaire for completion by teachers was used. RESULTS: Of the 988 questionnaires returned (71.5%), complete information concerning snoring was obtained for 976 children (496 girls and 480 boys; mean age: 8.1 +/- 1.5 years). Loud snoring during sleep was reported as frequent or constantly present (LSn) in 84 children (8.6%), as occasionally present in 299 children (30.6%), and as never present (NSn) by 593 children (60.8%). The LSn and NSn groups did not differ with respect to age, gender, sleep duration, time to fall asleep, frequency of night wakings, bedwetting, daytime tiredness, and school achievement. However, LSn was significantly associated with increased bedtime problems (fears and struggles), increased need for comforting activities to fall asleep, behaviors suggestive of parasomnias (sleep talking, teeth grinding, and night terrors), increased daytime sleepiness and irritability, and behavioral disturbances. Children in the LSn group were also more likely to report recurrent medical problems particularly those involving infections of the respiratory tract. CONCLUSIONS: Snoring is a common symptom in Portuguese children that is associated with behavioral daytime and sleep time disturbances. Children with loud snoring may benefit from early evaluation and intervention

Brazilian Bidens pilosa Linne´ yields fraction containing quercetin-derived flavonoid with free radical scavenger activity and hepatoprotective effects

Bidens pilosa is a plant used by Amazonian and Asian folks for some hepatopathies. The hydroethanol crude extract and three fractions were assessed for antioxidant and hepatoprotective effects. Higher levels of scavenger activity on the 1,1-diphenyl-2-picrylhydrazyl radical, inhibition of deoxyribose oxidation and lipid peroxidation in vitro were detected for the ethyl acetate fraction (IC50∼4.3-32.3 mg/ml) followed by the crude extract (IC50∼14.2-98.0 mg/ml). The ethyl acetate fraction, again followed by the crude extract, showed high contents of total soluble polyphenols (3.6±0.2 and 2.1±0.2 GAE/mg, respectively) and presence of a quercetin-derived flavonoid identified as quercetin 3,3′-dimethyl ether 7-Ο-β-D-glycopyranoside. Both products were assayed for hepatoprotector effects against CCl4-induced liver injury in mice. Markers of oxidative stress and hepatic injury were evaluated. The results showed that the 10-day pretreatments (15 mg/kg, p.o.) protected the livers against injury by blocking CCl4-induced lipid peroxidation and protein carbonylation and the DNA fragmentation was decreased (∼60%). The pretreatments avoided the loss of the plasma ferric reducing/antioxidant power and the elevation of serum transaminases and lactate dehydrogenase activities. The results suggest that the main constituents responsible for the hepatoprotective effects with free radical scavenger power associated are well extracted by performing fractionation with ethyl acetate. The findings support the Brazilian traditional use of this plant and justify further evaluations for the therapeutic efficacy and safety of the constituents of the ethyl acetate fraction to treat some liver diseases.Keywords: Bidens pilosa L.; hydroethanol maceration; ethyl acetate fractionation; free radical scavenger; hepatoprotection; CCl4 toxicit

Combination of cyclic nucleotide modulators with P2Y12 receptor antagonists as anti-platelet therapy

"This is the peer reviewed version of the following article: Armstrong, PC, Ferreira, PM, Chan, MV, et al. Combination of cyclic nucleotide modulators with P2Y12 receptor antagonists as anti‐platelet therapy. J Thromb Haemost. 2020 https://doi.org/10.1111/jth.14826 which has been published in final form at   https://doi.org/10.1111/jth.14826BACKGROUND: Endothelium-derived prostacyclin and nitric oxide elevate platelet cyclic nucleotide levels and maintain quiescence. We previously demonstrated that a synergistic relationship exists between cyclic nucleotides and P2Y12 receptor inhibition. A number of clinically approved drug classes can modulate cyclic nucleotide tone in platelets including activators of NO-sensitive guanylyl cyclase (GC) and phosphodiesterase (PDE) inhibitors. However, the doses required to inhibit platelets produce numerous side effects including headache. OBJECTIVE: We investigated using GC-activators in combination with P2Y12 receptor antagonists as a way to selectively amplify the anti-thrombotic effect of both drugs. METHODS: In vitro light transmission aggregation and platelet adhesion under flow were performed on washed platelets and platelet rich plasma. Aggregation in whole blood and a ferric chloride-induced arterial thrombosis model were also performed. RESULTS: The GC-activator BAY-70 potentiated the action of the P2Y12 receptor inhibitor prasugrel active metabolite in aggregation and adhesion studies and was associated with raised intra-platelet cyclic nucleotide levels. Furthermore, mice administered sub-maximal doses of the GC activator cinaciguat together with the PDE inhibitor dipyridamole and prasugrel, showed significant inhibition of ex vivo platelet aggregation and significantly reduced in vivo arterial thrombosis in response to injury without alteration in basal carotid artery blood flow. CONCLUSIONS: Using in vitro, ex vivo, and in vivo functional studies, we show that low dose GC activators synergize with P2Y12 inhibition to produce powerful anti-platelet effects without altering blood flow. Therefore, modulation of intra-platelet cyclic nucleotide levels alongside P2Y12 inhibition can provide a strong, focused anti-thrombotic regimen while minimizing vasodilator side effects

Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant

Introduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals. Case presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene. Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk

Mitochondrial-dependent apoptosis in Huntington's disease human cybrids

We investigated the involvement of mitochondrial-dependent apoptosis in Huntington's disease (HD) vs. control (CTR) cybrids, obtained from the fusion of human platelets with mitochondrial DNA-depleted NT2 cells, and further exposed to 3-nitropropionic acid (3-NP) or staurosporine (STS). Untreated HD cybrids did not exhibit significant modifications in the activity of mitochondrial respiratory chain complexes I-IV or in mtDNA sequence variations suggestive of a primary role in mitochondrial susceptibility in the subpopulation of HD carriers studied. However, a slight decrease in mitochondrial membrane potential and increased formation of intracellular hydroperoxides was observed in HD cybrids under basal conditions. Furthermore, apoptotic nuclei morphology and a moderate increase in caspase-3 activation, as well as increased levels of superoxide ions and hydroperoxides were observed in HD cybrids upon 3-NP or STS treatment. 3-NP-evoked apoptosis in HD cybrids involved cytochrome c and AIF release from mitochondria, which was associated with mitochondrial Bax translocation. CTR cybrids subjected to 3-NP showed increased mitochondrial Bax and Bim levels and the release of AIF, but not cytochrome c, suggesting a different mode of cell death, linked to the loss of membrane integrity. Additionally, increased mitochondrial Bim and Bak levels, and a slight release of cytochrome c in untreated HD cybrids may help to explain their moderate susceptibility to mitochondrial-dependent apoptosi

Review of Piezoelectrical Materials Potentially Useful for Peripheral Nerve Repair

It has increasingly been recognized that electrical currents play a pivotal role in cell migration and tissue repair, in a process named "galvanotaxis". In this review, we summarize the current evidence supporting the potential benefits of electric stimulation (ES) in the physiology of peripheral nerve repair (PNR). Moreover, we discuss the potential of piezoelectric materials in this context. The use of these materials has deserved great attention, as the movement of the body or of the external environment can be used to power internally the electrical properties of devices used for providing ES or acting as sensory receptors in artificial skin (e-skin). The fact that organic materials sustain spontaneous degradation inside the body means their piezoelectric effect is limited in duration. In the case of PNR, this is not necessarily problematic, as ES is only required during the regeneration period. Arguably, piezoelectric materials have the potential to revolutionize PNR with new biomedical devices that range from scaffolds and nerve-guiding conduits to sensory or efferent components of e-skin. However, much remains to be learned regarding piezoelectric materials, their use in manufacturing of biomedical devices, and their sterilization process, to fine-tune their safe, effective, and predictable in vivo application.info:eu-repo/semantics/publishedVersio

X-Linked Immunodeficient Mice With No Functional Bruton's Tyrosine Kinase Are Protected From Sepsis-Induced Multiple Organ Failure

We previously reported the Bruton's tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib improve outcomes in a mouse model of polymicrobial sepsis. Now we show that genetic deficiency of the BTK gene alone in Xid mice confers protection against cardiac, renal, and liver injury in polymicrobial sepsis and reduces hyperimmune stimulation (“cytokine storm”) induced by an overwhelming bacterial infection. Protection is due in part to enhanced bacterial phagocytosis in vivo, changes in lipid metabolism and decreased activation of NF-κB and the NLRP3 inflammasome. The inactivation of BTK leads to reduced innate immune cell recruitment and a phenotypic switch from M1 to M2 macrophages, aiding in the resolution of sepsis. We have also found that BTK expression in humans is increased in the blood of septic non-survivors, while lower expression is associated with survival from sepsis. Importantly no further reduction in organ damage, cytokine production, or changes in plasma metabolites is seen in Xid mice treated with the BTK inhibitor ibrutinib, demonstrating that the protective effects of BTK inhibitors in polymicrobial sepsis are mediated solely by inhibition of BTK and not by off-target effects of this class of drugs