Rapid and noninvasive technique to assess the metabolomics profile of bovine embryos produced in vitro by Raman spectroscopy

Morphological assessments are used to select embryos with the highest implantation potential, however it is still very limited. The development of new technologies, such as Raman spectroscopy have improved quantitative and qualitative analysis, and consequently led to a better characterization of embryos and improvements on the prediction of their potential. Therefore, we propose a method based on the conventional in vitro culture system of bovine embryos, and the subsequent analysis of the culture media drops by Raman spectroscopy. Our results obtained by PCA analysis clearly showed a separation of the spectral profiles from culture media drops with and without embryos.OCIS codes: (170.0170) Medical optics and biotechnology, (170.5660) Raman spectroscopy, (170.1420) Biology     

Heteroresistance to Itraconazole Alters the Morphology and Increases the Virulence of Cryptococcus gattii

Cryptococcus gattii is the main etiological agent of cryptococcosis in immunocompetent individuals. The triazole drug itraconazole is one of the antifungals used to treat patients with cryptococcosis. Heteroresistance is an adaptive mechanism to counteract the stress of increasing drug concentrations, and it can enhance the ability of a microorganism to survive under antifungal pressure. In this study, we evaluated the ability of 11 C. gattii strains to develop itraconazole heteroresistance. Heteroresistant clones were analyzed for drug susceptibility, alterations in cell diameter, capsule properties, and virulence in a murine model. Heteroresistance to itraconazole was intrinsic in all of the strains analyzed, reduced both the capsule size and the cell diameter, induced molecular heterogeneity at the chromosomal level, changed the negatively charged cells, reduced ergosterol content, and improved the antioxidant system. A positive correlation between surface/volume ratio of original cells and the level of heteroresistance to itraconazole (LHI) was observed in addition to a negative correlation between capsule size of heteroresistant clones and LHI. Moreover, heteroresistance to itraconazole increased the engulfment of C. gattii by macrophages and augmented fungal proliferation inside these cells, which probably accounted for the reduced survival of the mice infected with the heteroresistant clones and the higher fungal burden in lungs and brain. Our results indicate that heteroresistance to itraconazole is intrinsic and increases the virulence of C. gattii. This phenomenon may represent an additional mechanism that contributes to relapses of cryptococcosis in patients during itraconazole therapy.     

The crowding effect in Ancylostoma ceylanicum: density-dependent effects on an experimental model of infection

This study compared the course of Ancylostoma ceylanicum infection in hamsters infected with different inocula and the consequences for the host and helminth populations. The average of adult worms recovered, according to the number of third stage larva used, were 28.0, 24.8, 24.6, and 24.8 % to inocula size of 25 L3, 75 L3, 125 L3, and 250 L3, respectively. The size of the inoculum did not affect the establishment, survival, or fecundity of adult helminths. Reductions in the red blood cell and hemoglobin levels in the infected group were inversely proportional to the number of white blood cells. Moreover, differential cell counting revealed a positive correlation between the worm load and leucocyte numbers. The humoral response against excretion-secretion antigens was more robust and sensitive compared with the response against crude extract, with no direct linear correlation with the number of worms. The effect of the population density was more evident in females.     

Virtual chromoendoscopy in small bowel capsule endoscopy: New light or a cast of shadow?

AIM: To evaluate whether virtual chromoendoscopy can improve the delineation of small bowel lesions previously detected by conventional white light small bowel capsule endoscopy(SBCE). METHODS: Retrospective single center study. One hundred lesions selected from forty-nine consecutive conventional white light SBCE(SBCE-WL) examinations were included. Lesions were reviewed at three Flexible Spectral Imaging Color Enhancement(FICE) settings and Blue Filter(BF) by two gastroenterologists with ex-perience in SBCE, blinded to each other's findings, whoranked the quality of delineation as better, equivalent or worse than conventional SBCE-WL. Inter-observer percentage of agreement was determined and analyzed with Fleiss Kappa(k) coefficient. Lesions selected for the study included angioectasias(n = 39), ulcers/ero-sions(n = 49) and villous edema/atrophy(n = 12). RESULTS: Overall, the delineation of lesions was im-proved in 77% of cases with FICE 1, 74% with FICE 2, 41% with FICE 3 and 39% with the BF, with a percent-age of agreement between investigators of 89%(k = 0.833), 85%(k = 0.764), 66%(k = 0.486) and 79%(k = 0.593), respectively. FICE 1 improved the delineation of 97.4% of angioectasias, 63.3% of ulcers/erosions and 66.7% of villous edema/atrophy with a percentage of agreement of 97.4%(k = 0.910), 81.6%(k = 0.714) and 91.7%(k = 0.815), respectively. FICE 2 improved the delineation of 97.4% of angioectasias, 57.1% of ulcers/erosions and 66.7% of villous edema/atrophy, with a percentage of agreement of 89.7%(k = 0.802), 79,6%(k = 0.703) and 91.7%(k = 0.815), respectively. FICE 3 improved the delineation of 46.2% of angioecta-sias, 24.5% of ulcers/erosions and none of the cases of villous edema/atrophy, with a percentage of agreement of 53.8% [k = not available(NA)], 75.5%(k = NA) and 66.7%(k = 0.304), respectively. The BF improved the delineation of 15.4% of angioectasias, 61.2% of ulcers/erosions and 25% of villous edema/atrophy, with a per-centage of agreement of 76.9%(k = 0.558), 81.6%(k = 0.570) and 25.0%(k = NA), respectively.CONCLUSION: Virtual chromoendoscopy can improve the delineation of angioectasias, ulcers/erosions and villous edema/atrophy detected by SBCE, with almost perfect interobserver agreement for FICE 1.     

FACTORS ASSOCIATED TO ADHERENCE TO DIFFERENT TREATMENT SCHEMES WITH MEGLUMINE ANTIMONIATE IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.     

Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

Background

The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea.

Objective

To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample.

Methods

Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart®) system.

Results

A total of 767 participants (461 men) with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat) was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001). After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia.

Conclusion

Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample.     

Securing sustainable funding for viral hepatitis elimination plans

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct‐acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries’ health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro‐elimination approach in specific populations is less complex and less costly than country‐wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO.     

Human herpesvirus 6 is associated with status epilepticus and hyponatremia after umbilical cord blood transplantation

Status epilepticus after allogeneic hematopoietic cell transplantation (alloHCT) is rare. The authors report a case involving a 65-year-old man with nonconvulsive status epilepticus 34 days after umbilical cord blood transplantion for chronic lymphocytic leukemia. Cerebrospinal fluid and serum were positive for human herpesvirus 6 (HHV6). Magnetic resonance imaging of the brain showed symmetric T2 hyper-intensity bilaterally in the mesial temporal lobes, and T2 hyperintensi-ties and restricted diffusion of bilateral putamina. Despite aggressive anticonvulsive therapy, his seizures only abated with initiation of ganciclovir therapy. The patient completed six weeks of combination antiviral therapy (ganciclovir and foscarnet). His cognitive function gradually improved and, after prolonged rehabilitation, the patient was discharged home with residual intermittent memory loss but otherwise functional. HHV6 should be considered in the differential diagnosis of nonconvulsive status epilepticus after alloHCT, especially in patients with hyponatremia. Empirical antiviral therapy targeting HHV6 should be administered to these patients.