Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.     

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser⁸⁴⁵ in the Ctx and GluR1-Ser⁸³¹ in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.     

Role of the extracellular matrix in variations of invasive pathways in lung cancers

Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor β (TGF-β) may favor invasion, cellular motility, and proliferation. We examined HAase proteins (Hyal), HAS, E-cadherin, and TGF-β profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P < 0.01). Stroma cells of SqCC from non-smokers presented a significant association with HAS-3 (P < 0.01). Hyal, HAS, E-cadherin, and TGF-β modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-β and E-cadherin, may have a greater impact in lung cancer prognosis.     

Perceptions of Families of Individuals with Autism Spectrum Disorder during the COVID-19 Crisis

Caring for an individual with autism spectrum disorder (ASD) in ideal circumstances can be stressful, and the Coronavirus disease (COVID-19) pandemic created a high degree of disruption to life and stress to families living with an individual with ASD. We conducted an online survey of families in Michigan that revealed higher levels of stress in caregivers of younger individuals with ASD and those with greater severity of ASD symptoms. Stress around therapeutic service disruption, finances, and illness predominated and greater stress was reported for caregivers of individuals receiving greater intensity of services pre-COVID-19. Respondents voiced concerns about receiving respite care during COVID-19, and those expressing interest in respite also reported greater symptom severity in the person with ASD.

     

ABO blood group in Amerindians from Brazilian Amazon

Background : The Parakanã is a group of Indians with cultural similarities to the extinct Tupi group. They are an isolated native population from East Brazilian Amazon. A number of different O alleles have been found at the blood group ABO locus in populations of several ethnic origins (Caucasians, Blacks, Amerindians). Aim : The present study describes the ABO blood group polymorphism gene of the Parakanã Indians. The Amerindian group was carefully selected for racial background. Subject and methods : The blood group polymorphism was analysed in genomic DNA from 62 Parakanã Indians. We determined the 261G deletion, the T646A and C771T mutations described in O 1variant and the G542A substitution, using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Results : All Amerindians studied were homozygous for the 261G deletion. The frequencies of the T646A and C771T mutations in Parakanãs (0.65) were lower than that observed in Kayapo, Yanomama and Arara Indians (0.91) ( &#104 2 = 18.24; p-v < 0.001. The G542A substitution in Parakanãs was also lower (0.22) than in other tribes (0.42) ( &#104 2 = 9.73; p-v = 0.001). Conclusions : The different O alleles including the G542A mutation are not distributed homogeneously among all Amazonian Amerindians. Our results are in agreement with other genetic markers studied previously in Parakanã Indians, whose distinct genetic pattern differs from Europeans and even from other Amerindians.     

Risk factors for neurological complications in children with Flavivirus infection

Journal of NeuroVirology - This study aims to characterize the acute neurological manifestations caused by DENV, ZIKV, and YFV during hospitalization; identify the risk factors associated with...     

An introduction of the role of probiotics in human infections and autoimmune diseases

Abstract

During the last decades, studies exploring the role of microorganisms inhabiting human body in different scenarios have demonstrated the great potential of modulating them to treat and prevent diseases. Among the most outstanding applications, probiotics have been used for over a century to treat infections and inflammation. Despite the beneficial role of other probiotics, Lactobacillus and Bifidobacterium species are the most frequently used, and have been effective as a therapeutic option in the treatment/prevention of dental caries, periodontal diseases, urogenital infections, and gastrointestinal infections. Additionally, as gastrointestinal tract harbors a great diversity of microbial species that directly or indirectly modulate host metabolism and immune response, the influence of intestinal microbiota, one of the targets of therapies using probiotics, on the biology of immune cells can be explored to treat inflammatory disorders or immune-mediated diseases. Thus, it is not surprising that probiotics have presented promising results in modulating human inflammatory diseases such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease, among others. Hence, the purpose of this review is to discuss the potential of therapeutic approaches using probiotics to constrain infection and development of inflammation on human subjects.     

Periodontal clinical status,microbial profile,and expression of interleukin-1β in men under androgenic anabolic steroids abuse

Clinical Oral Investigations - Androgenic anabolic steroids (AAS) abuse is a serious health problem associated to several systemic complications. Here, we evaluated the periodontal clinical status,...