Features of aminopropyl modified mesoporous silica nanoparticles. Implications on the active targeting capability

Aminopropyl modified mesoporous SiO2 nanoparticles, MCM-41 type, have been synthesized by the co-condensation method from tetraethylorthosilicate (TEOS) and aminopropyltriethoxysilane (APTES). By means of modifying TEOS/APTES ratio we have carried out an in-depth characterization of the nanoparticles as a function of APTES content. Surface charge and nanoparticles morphology were strongly influenced by the amount of APTES and particles changed from hexagonal to bean-like morphology insofar APTES increased. Besides, the porous structure was also affected, showing a contraction of the lattice parameter and pore size, while increasing the wall thickness. These results bring about new insights about the nanoparticles formation during the co-condensation process. The model proposed herein considers that different interactions stablished between TEOS and APTES with the structure directing agent have consequences on pore size, wall thickness and particle morphology. Finally, APTES is an excellent linker to covalently attach active targeting agents such as folate groups. We have hypothesized that APTES could also play a role in the biological behavior of the nanoparticles. So, the internalization efficiency of the nanoparticles has been tested with cancerous LNCaP and non-cancerous preosteoblast-like MC3T3-E1 cells. The results indicate a cooperative effect between aminopropylsilane presence and folic acid, only for the cancerous LNCaP cell line

Effects of Milled Maize Stalks on the Productive Response of Grazing Dairy Cows.

The productive response of grazing dairy cows was evaluated, using milled corn stalks in the diet. The study was developed in two different settings, in Ecuador (Costa and Sierra regions). On the coast farm (29.1 ha), cows grazed on Bermuda grass (Cynodon nlemfuensis) and Guinea grass (Panicum maximum) with several types of legumes (Lysicarpus, Centrosema, Desmodium, Galactia), supplemented with corn stalks cv. INIAP 125. The animals received 0.46 kg beginning at 3 kg, and milled maize stalks in 30 and 28-day periods, respectively (M-30 and M-28), and control without stalks for 36 days (M-0). The farm in the other region (14.2 ha) had 23 cows grazing on Kikuyo grass (P. clandestinum) and ryegrass-white clover (L. perenne and whole maize stalks and T. (60-70% ripe grain), at a rate of 18 kg green/cow/day for 48 days; and balanced supplement, at a rate of 0.5 kg/ milk liter, after the fourth kilogram, along with minerals. In both cases the forage had effects (P < 0.05) on cow response. In the Sierra area, the increase was 1.68 kg/cow, and in the coast, it was 1.1 and 2.5 kg/cow). Maize stalks served as a nutritional complement for poorly consumed grass areas in both regions; milk production/animal was increased, and the costs were reduced

Efecto de la inclusión del forraje de maíz molido en la respuesta productiva de vacas lecheras en pastoreo.

Se evaluó la respuesta productiva de vacas lecheras en pastoreo al incluir forraje de maíz molido en su dieta. El estudio se realizó en dos ambientes diferentes de Ecuador (Región Costa y Sierra). En la costa, en una finca de 29,1 ha,las vacas pastaron asociaciones de estrella (Cynodon nlemfuensis) y saboya (Panicum máximum) con leguminosas devarios géneros como Alysicarpus, Centrosema, Desmodium, Galactia, suple-mentadas con forraje de maíz cv. INIAP 125. Los animales recibieron 0,46 kg a partir del tercer kilogramo, y forraje de maíz molido en períodos de 30 y 28 días, respectivamente (M-30 y M-28) y control sin forraje por 36 días (M-0). En la otra región, la propiedad tenía 14,2 ha y 23 vacas en ordeño; estas pastaron asociaciones de kikuyo (P. clandestinum) y ryegra-sstrébol blanco (L. perenne y T. repens) y forraje de maíz planta completa (60 a 70 % grano maduro), a razón de 18 kg verde/vaca/día durante 48 días, y balanceado a razón de 0,5 kg/l de leche después del cuarto kilogramo y minerales. El forraje influyó en ambos casos (P < 0,05) en la respuesta de las vacas; para la zona de la sierra el incremento fue de 1,68 kg/vaca de aumento en la leche y en la costa el aumento fue entre 1,1 y 2,5 kg/vaca. El forraje de maíz complementó nutri-cionalmente las asociaciones bajo pastoreo en ambas regiones, incrementó el rendimiento lechero/animal y redujo los costos.Effect of Ground CornStalks on the Productive Response of Dairy Grazing Cows ABSTRACTThe productive response of dairy grazing cows using ground cornstalks was assessed. The study was developed in two different Ecuadoran settings (Costa Region and Sierra). At the Costa, on a 29.1 ha farm, the cows grazed on star clusters (Cynodon nlemfuensis) and panic grass(Panicum máximum), with legumes of different genera, such as Alysicarpus, Centrosema, Desmodium, Galactia, supplemented with corn stalks, cv. INIAP 125. The animals received 0.46 kg from the third kg onward, and ground corn stalks in 30- and 28- day periods, respectively (M-30 and M-28), and a control group without stalks for 36 days (M-0). In another region, the estate had 14.2 ha and 23 milking cows, grazing on clusters of West African pennisetum (P. clandestinum) and ryegrass white clover (L. perenne and T. repens) and whole corn stalks (60 -70 % ripe grain), at a ratio of 18 kg green/cow/day for 48 days and balanced at a ratio of 0.5 kg/l of milk following the fourth kilogram, and minerals. In both cases, stalks effected (P < 0.05) on cow response. In the Sierra region, the milk yield increase observed was 1.68 kg/cow, and in the Costa region, it was between 1.1 and 2.5 kg/cow. Corn stalks meant nutritional supplementation to grazing clusters in both regions, increased milk/animal yields, and cost reductions

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years