The marine toxin dinophysistoxin-2 induces differential apoptotic death of rat cerebellar neurons and astrocytes.

Diarrhetic shellfish poisoning (DSP) toxins of algal origin are frequent contaminants of coastal waters and seafood. The potential risk for human health due to the continuous presence of these toxins in food has not been clearly established. We have used cerebellar primary cultures to investigate the effects of the DSP toxin dinophysistoxin-2 (DTX-2) on central nervous system neurons and glial cells. Exposure to DTX-2 produced neurotoxicity at concentrations starting at 2.5 nM, characterized first by disintegration of neurites and later by cell death. DTX-2-induced neurodegeneration required long exposures (at least 20 h), involved DNA fragmentation and condensation and fragmentation of chromatin, typical hallmarks of apoptosis, and required the synthesis of new proteins. The concentration that reduced by 50% the maximum neuronal survival after 24 h exposure to DTX-2 (EC50(24)) was approximately 8 nM. Morphology and viability of glial cells remained unaffected up to at least 15 nM DTX-2. Higher concentrations of the toxin caused strong shrinkage of glial cell bodies and retraction of processes, and a significant reduction of glial cell viability. Glial toxicity by DTX-2 involved typical apoptotic condensation and fragmentation of chromatin. Compared to neurons, the effect on glial cells was a much shorter process, and extensive glial degeneration and death occurred after 7 h exposure to DTX-2 (EC50(7) approximately 50 nM; EC50(24) approximately 30 nM). Although further experiments are needed to confirm these toxic actions in vivo, our in vitro data suggest that chronic exposure to amounts of DSP toxins below the current safety regulatory limits may represent a risk for human health that should be taken into consideration.     

An outbreak of cryptosporidiosis associated with drinking water in north-eastern Italy,August 2019: microbiological and environmental investigations

Cryptosporidium is a leading global cause of waterborne disease, with many reported outbreaks related to main water supplies. In August 2019, an outbreak of cryptosporidiosis involving 80 cases occurred among 114 vacationers in a small municipality located in the Tuscan-Emilian Apennines, north-eastern Italy. After excluding a potential food-borne outbreak, the epidemiological investigation focussed on the hypothesis of a waterborne outbreak. This was confirmed by the finding of Cryptosporidium oocysts in stools of the cases and in water samples from the municipal water network. Molecular characterisation revealed the zoonotic species Cryptosporidium parvum as the causative agent. A single subtype (IIdA25G1) was found among all cases, and in one of two positive water samples. The municipality’s water supply used spring water that only received a disinfection treatment insufficient to inactivate the parasite. Possible entry means into the water mains were found through further environmental investigations. As these types of water supplies are particularly vulnerable to various environmental factors, a control system based on the risk assessment of each phase of the water supply chain is required to guarantee water safety. Effective methods for detection of protozoan pathogens, which are generally excluded from routine water supply analysis, should be applied.     

Long-term survival of single versus bilateral internal mammary artery grafting in patients under 70

Open in a separate window OBJECTIVESAs definitive data from randomized controlled trials comparing the effect on long-term survival of using single internal mammary artery (SIMA) or bilateral internal mammary artery (BIMA) grafting are not yet available, observational studies allow for long-term follow-up in large and representative populations, which might complement the information potentially derived from randomized trials. To compare long-term survival in patients under 70 years of age undergoing SIMA or BIMA grafting.METHODSRetrospective analysis of 3384 consecutive patients under 70 years undergoing primary isolated coronary artery bypass grafting, performed from 2000 to 2015, in a Portuguese level III Hospital. We identified 2176 and 1208 patients from the study population who underwent SIMA and BIMA grafting, respectively. The primary end point was all-cause mortality at 10 years. We employed inverse probability weighting to restrict confounding by indication.RESULTSThe mean age of the study population was 59.4 (± 7.6) years, and 567 (16.8%) were females. Inverse probability weighting was effective in eliminating differences in all significant baseline characteristics. Follow-up was 99.88% complete. The median follow-up time was 12.82 (interquartile range, 9.65, 16.74) years: the primary end point of all-cause mortality at 10 years occurred in 463 patients (21.3%) and 166 (13.7%) in the SIMA and BIMA grafting groups, respectively (hazard ratio, 0.78; 95% confidence interval, 0.66–0.92; P = 0.004).CONCLUSIONSBilateral internal mammary grafting is associated with lower long-term mortality than single internal mammary grafting. Moreover, this survival benefit comes at no increased perioperative morbidity or mortality cost.     

Stereotactic Radiotherapy after Incomplete Transarterial (Chemo-) Embolization (TAE\TACE) versus Exclusive TAE or TACE for Treatment of Inoperable HCC: A Phase III Trial (NCT02323360)

Background: Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization (TAE/TACE) has shown a disease response in 15–55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses. Methods: This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE ({"type":"clinical-trial","attrs":{"text":"NCT02323360","term_id":"NCT02323360"}}NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications. Results: At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months, p = 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded. Conclusions: SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.     

Differential Effects of Three Nutritional Supplements on the Nutrient Intake of Pregnant Women Enrolled in a Conditional Cash Transfer Program in Mexico: A Cluster Randomized Trial

Supplementation in malnourished pregnant women should not displace natural healthy foods. Objective: To estimate the differential effects of three nutritional supplements on macro- and micronutrient intake of pregnant women beneficiaries of the conditional cash transfer program Prospera (CCT-POP). Methods: Prospective cluster randomized trial. Communities were randomly assigned to receive a fortified beverage (Beverage), micronutrient tablets (Tablets), or micronutrient powder (MNP). Pregnant women (at <25 weeks) were recruited. The food frequency questionnaire was applied at 25 and 37 weeks of pregnancy and at one and three months postpartum (mpp). Differential effects of the three supplements on the median change in nutrient intake from baseline to each follow-up stage were estimated. Results: Median change in protein intake from dietary and supplement sources were significantly lower for MNP and Tablets than for Beverages (baseline to 37 w: −7.80 ± 2.90 and −11.54 ± 3.00, respectively; baseline to 1 mpp: −7.34 ± 2.90 for MNP, p < 0.001). Compared to Beverages, median increases were higher for the MNP for vitamins C (31.2 ± 11.7, p < 0.01), E (1.67 ± 0.81, p < 0.05), and B12 (0.83 ± 0.27, p < 0.01) from baseline to 37 wk; from baseline to 1 mpp, there was a higher median increase in B12 (0.55 ± 0.25, p < 0.05) and folate (63.4 ± 24.3, p < 0.01); and from baseline to 3 mpp, a higher median increase in iron (2.38 ± 1.06, p < 0.05) and folate (94.4 ± 38.1, p < 0.05). Conclusions: Intake of micronutrients was higher for MNP and Tablets, likely due to food displacement among Beverage consumers. Although iron bioavailability and absorption inhibitors were not considered for the present analyses, the distribution of Tablets or MNP had several advantages in this context where micronutrient deficiency remains high among pregnant women, but macronutrient intake is generally adequate or even high.     

Intraoperative blood transfusion in pediatric patients undergoing renal transplant—Effect of renal graft size

In pediatric RT, donor allograft size often exceeds the expected recipient norms, especially in younger recipients. An “oversize” graft might not only present a technical‐ and space‐related challenge, but may possibly lead to increased demands in perioperative volume requirements due to the disparity between donor and recipient in renal blood flow. We evaluated transfusion practices at a single tertiary institution with special consideration of kidney graft size, hypothesizing that oversize graft kidneys might lead to a quantifiable increased need of blood transfusion in smaller recipients. Retrospective analysis of all patients who underwent pediatric RT from January 2004 to June 2014 at a tertiary pediatric centre was performed. Variables analyzed included patient age, weight, pre‐ and postoperative Hb concentration, graft size, EBL, amount of intraoperative blood transfusion, and preoperative use of erythropoietin. Based on graft size in relation to patient's age, a SMR and an OvR were identified. A subcohort of age‐matched pairs was used to allow for comparison between groups. We calculated the expected procedure‐ and transfusion‐induced changes in Hb and compared these changes to the observed difference in pre‐ vs postoperative Hb to assess the influence of graft size on transfusion requirements. RT was performed in 188 pediatric recipients during the study period. In the matched cohort, percentage of transfused patients during transplantation in the OvR group was more than double compared with SMR (89% vs 39%, P < .001); similarly, the median number of transfused PRBC units in OvR was 1, while the median of SMR did not receive transfusion (P < .001). The difference between expected (calculated) and observed change in Hb was significantly higher in OvR with a median of 1.9 g/dL compared with SMR with a median of 1.0 g/dL (P = .026). Correspondingly, the calculated median volume taken up by a regular size kidney was significantly higher with 213 mL compared with 313 mL (P = .031) taken up by an oversize graft kidney. Median estimated intraoperative blood loss was significantly higher in OvR than in SMR (6.9 mL/kg, vs 5.3 mL/kg, respectively; P = .04). Median postoperative Hb was similar among groups (10.4 g/dL vs 10.6 g/dL for SMR vs OvR, respectively). Transplantation of an oversized kidney in pediatric RT recipients is associated with a quantifiable higher need for blood transfusion. This may be caused by a higher intraoperative EBL and/or greater blood volume sequestered by the larger renal allograft and requires further evaluation.     

Dealumination and Characterization of Natural Mordenite-Rich Tuffs

The present study evaluates the feasibility of partially dealuminated natural mordenite as a catalyst support by studying improvement in its textural properties. This is the first study that reports the dealumination of natural zeolite-based tuffs from Ecuador. For this purpose, mordenite-rich tuffs were obtained from deposits close to Guayaquil, Ecuador. The raw material was micronized in order to increase its surface, and treated with NH₄Cl. NH₄⁺ cation-exchanged samples were finally reacted with HCl_(aq) to complete the dealumination process. The partially dealuminated samples were characterized using techniques such as XRD, FT-IR, SEM-EDS, and identification of their textural properties. Dealumination with HCl_(aq) increased the Si/Al ratio up to 9 and kept the crystallographic structure of natural mordenite, as XRD results showed that the structure of mordenite was not altered after the dealumination process. On the other hand, textural properties such as surface area and microporosity were improved as compared to natural mordenite. In view of these results, the feasibility of using natural mordenite as a catalyst support is discussed in this study.     

Alcance das Metas de Colesterol LDL após Infarto Agudo do Miocárdio: Dados Reais do Sistema Público de Saúde da Cidade de Curitiba

BackgroundReduction of LDL-cholesterol (LDL-c) levels is the cornerstone in risk reduction, but many high-risk patients are not achieving the recommended lipid goals, even in high-income countries.ObjectiveTo evaluate whether patients seen in the city of Curitiba public health system are reaching LDL-c goals after an acute myocardial infarction (AMI).MethodsThis retrospective cohort explored the data of patients admitted with AMI between 2008 and 2015 in public hospitals from the city of Curitiba. In order to evaluate the attainment of the LDL-c target, we have used the last value registered in the database for each patient up to 2016. For those who had at least one LDL-c registered in the year before AMI, percentage of reduction was calculated. The level of significance adopted for statistical analysis was p<0.05.ResultsOf 7,066 patients admitted for AMI, 1,451 were followed up in an out-patient setting and had at least one evaluation of LDL-c. Mean age was 60.8±11.4 years and 35.8%, 35.2%, 21.5%, and 7.4% of patients had LDL-c levels ≥100, 70–99, 50–69 and <50 mg/dL, respectively. Of these, 377 patients also had at least one LDL-c evaluation before the AMI. Mean LDL-c concentrations were 128.0 and 92.2 mg/dL before and after AMI, with a mean reduction of 24.3% (35.7 mg/dL). LDL-c levels were reduced by more than 50% in only 18.3% of the cases.ConclusionIn the city of Curitiba public health system patients, after myocardial infarction, are not achieving adequate LDL-c levels after AMI.     

Albendazole and its derivative JVG9 induce encystation on Giardia intestinalis trophozoites

In the present study, we evaluated the effect of an albendazole (ABZ) derivative JVG9 on cultured Giardia intestinalis. To assess the JVG9 effects, we evaluated the tubulin cytoskeleton by confocal microscopy, and we found that the characteristic staining was modified. The scanning electron microscopy images revealed extremely damaged trophozoites and cyst-like cells. The confocal images revealed that this drug triggered the expression of cyst wall protein 1 and encystation. We also found that at low doses, AL triggered the encystation process too.