Estimating the savings of a national project to prevent healthcare-associated infections in intensive care units.

BACKGROUND: Healthcare-associated infections (HAIs) have a significant impact on patients' morbidity and mortality, and have a detrimental financial impact on the healthcare system. Various strategies exist to prevent HAIs, but economic evaluations are needed to determine which are most appropriate. AIM: To present the financial impact of a nationwide project on HAI prevention in intensive care units (ICUs) using a quality improvement (QI) approach. METHODS: A health economic evaluation assessed the financial results of the QI initiative 'Saúde em Nossas Mãos' (SNM), implemented in Brazil between January 2018 and December 2020. Among 116 participating institutions, 13 (11.2%) fully reported the aggregate cost and stratified patients (with vs without HAIs) in the pre-intervention and post-intervention periods. Average cost (AC) was calculated for each analysed HAI: central-line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTIs). The absorption model and time-driven activity-based costing were used for cost estimations. The numbers of infections that the project could have prevented during its implementation were estimated to demonstrate the financial impact of the SNM initiative. RESULTS: The aggregated ACs calculated for each HAI from these 13 ICUs - US$8480 for CLABSIs, US$10,039 for VAP, and US$7464 for CAUTIs - were extrapolated to the total number of HAIs prevented by the project (1727 CLABSIs, 3797 VAP and 2150 CAUTIs). The overall savings of the SNM as of December 2020 were estimated at US$68.8 million, with an estimated return on investment (ROI) of 765%. CONCLUSION: Reporting accurate financial data on HAI prevention strategies is still challenging in Brazil. These results suggest that a national QI initiative to prevent HAIs in critical care settings is a feasible and value-based approach, reducing financial waste and yielding a significant ROI for the healthcare system.

High resilience of campos rupestres plants to the interaction of drought and fire.

The concurrent impacts of multiple disturbances have the potential to modify ecosystem functioning by diminishing recovery capacity and resilience. Nevertheless, it remains uncertain how plant species from tropical communities respond to the cumulative effects of drought and fire. In this study, we evaluated the responses of six plant species from campos rupestres subjected to a mild drought followed by fire and tested if plants subjected to simulated drought show reductions in carbon uptake and depletion of non-structural carbohydrate (NSC) reserves, thus constraining their resprouting. We monitored monthly variations in leaf gas exchange and aboveground biomass over 18 months. Subsequently, an accidental fire occurred in the study area, leading us to collect samples of belowground structures for NSC analyses on the day of the burn. There were no differences in the frequency of resprouting between the above two conditions. Additionally, gas exchange in most species either remained stable or increased after the fire. Drought had no adverse effects on NSC reserves in the belowground structures and may have contributed to species resprouting after fire. The impact of drought pre-conditions on post-fire aboveground biomass was generally minor for most species, except Vellozia nivea, which displayed roughly a 5% reduction in biomass following the drought. Our findings highlight the remarkable resilience of campos rupestres species, even after enduring 18 months of reduced water availability and an unintended fire event. These species demonstrated the capacity to maintain their physiological functions and resprouting capacities after a fire event, underscoring their strong recovery potential.

24-Epibrassinolide alleviates drought effects in young Carapa guianensis plants, improving the hydraulic safety margin, gas exchange and antioxidant defence.

Climate change is increasing the frequency of extreme events such as droughts, limiting plant growth and productivity. Exogenous application of plant growth regulators, such as 24-epibrassinolide (EBR), might be a solution as this molecule is organic, eco-friendly, and biodegradable. This is the first research to examine possible roles of EBR on the hydraulic safety margin, physiological behaviour, and metabolism in Carapa guianensis Aubl. (Meliaceae) exposed to drought. C. guianensis is a widely distributed tree in tropical forests of the Amazon. The objective was to determine whether EBR can improve tolerance to water deficit in young C. guianensis by measuring hydraulic traits, nutritional, biochemical and physiological responses, and biomass. The experiment had four randomized treatments: two water conditions (control and water deficit) and two concentrations of EBR (0 and 100 nM EBR). EBR increased the water potential and hydraulic safety margin, increased CO2 fixation, and improved stomatal performance. EBR also stimulated antioxidant defences (SOD, CAT, APX, and POX). Overall, tretreatment with EBR improved drought tolerance of young C. guianensis plants.

Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

Timed artificial insemination plus heat I: effect of estrus expression scores on pregnancy of cows subjected to progesterone-estradiol-based protocols.

Expression of estrus near timed artificial insemination (TAI) is associated with greater fertility, and estrus detection could improve TAI fertility or direct TAI management, although accurate estrus detection can be difficult and time-consuming using traditional methods. The aim of this study is to evaluate influence of estrus on pregnancy (artificial insemination pregnancy rates (P/AI)) and to validate an alternative method to classify estrus/heat expression using tail chalking (HEATSC) in postpartum Bos indicus cows subjected to TAI in progesterone-estrogen-based protocols. In experiment 1 (Exp. 1), cows (5491) were subjected to visual observation of estrus after progesterone device removal, before TAI, and P/AI was evaluated according to estrus and body condition score (BCS). Cows received a progesterone device and 2 mg estradiol benzoate (EB). After 8 days, the device was removed and 150 µg of d-cloprostenol and 300 IU equine chorionic gonadotrophin was given. Later, animals in Exp. 1 received 1 mg EB and TAI 44 to 48 h. In the Exp. 2 - 3830 cows using similar protocol, received different ovulation inducers: 1 mg EB (n=1624) or 1 mg estradiol cypionate (EC; n=2206) on day 8 (D8). Cows were then marked with chalk, and HEATSC evaluated at TAI on D10 (HEATSC1 - no chalk removal=no estrus expression; HEATSC2 - partial chalk removal=low estrus expression; HEATSC3 - near complete/complete chalk removal=high estrus expression). In Exp. 1, cows showing estrus presented greater P/AI (48.4% v. 40.2%, P<0.05). In Exp. 2, P/AI (HEATSC1 - 40.0%; HEATSC2 - 49.7%; HEATSC3 - 60.9%; P<0.001), and larger follicle timed artificial insemination (LFTAI) (<0.001) varied according to HEATSC. There was no difference in P/AI (P=0.41) or LFTAI (P=0.33) according to ovulation inducer. Cows with greater BCS showed greater P/AI in both experiments (P<0.05). Estrus presence and greater HEATSC improved P/AI, and EC v. EB used promoted differential estrus manifestation (cows showing HEATSC2 and HEATSC3: 79.5% with EB v. 69.98% with EC use, P<0.001), however, with similar P/AI. The use of HEATSC in B. indicus cows subjected to TAI is useful to identify cows with greater estrus expression and consequently improved pregnancy rates in TAI, allowing the cows with low HEATSC to be targeted for additional treatments aimed at improving P/AI.

Timed artificial insemination plus heat II: gonadorelin injection in cows with low estrus expression scores increased pregnancy in progesterone/estradiol-based protocol.

The use of tail chalk and estrus/heat expression scores (HEATSC) evaluation is instrumental in identifying cows with greater estrus expression and greater artificial insemination pregnancy rates (P/AI) in cows submitted to timed artificial insemination (TAI), and cows with low or no estrus expression present lower P/AI. It was intended in this study to improve the pregnancy rates in TAI for Bos indicus beef cows, and gonadotrophin-releasing hormone (GnRH) injection was hypothesized to increase pregnancy rates in a TAI program for cows submitted to progesterone-estradiol-based protocols with low or no estrus expression, evaluated by HEATSC. Cows (n= 2284) received a progesterone device and 2 mg estradiol benzoate, after 8 days the device was removed and 1 mg estradiol cypionate, 150 µg of d-cloprostenol and 300 IU equine chorionic gonadotropin was administered. All cows were marked with chalk and HEATSC evaluated (scales 1 to 3) at TAI performed on day 10. Animals with HEATSC1 and HEATSC2 (n= 937) received 100 µg de gonadorelin (GNRH group; n= 470), or 1 ml saline (Control group; n= 467), and cows with HEATSC3 (named HEAT group; n= 1347) received no additional treatment. The larger dominant follicle, evaluated on day 8and at TAI (day 10), was greater in HEAT group (P= 0.0145 and P <0.001, respectively). Corpus luteum (CL) area and progesterone concentration was evaluated on day 17, and CL area was larger in HEAT group, intermediary in Control and lower in GnRH group (Control= 2.68 cm2, GnRH= 2.37 cm2, HEAT group= 3.07 cm2, P <0.001). Greater progesterone concentrations were found in HEAT group than in Control and GnRH groups (Control= 4.74 ng/ml, GnRH= 4.29 ng/ml, HEAT group= 6.08 ng/ml, P<0.001). There was a difference in ovulation rate, greater in HEAT group than GnRH and Control groups (Control= 72.5%; GnRH= 81.25%; HEAT group= 90.71%; P= 0.0024). Artificial insemination pregnancy rates was greater in HEAT group (57.09% (769/1347) than in Control and GNRH groups, with positive effect of GnRH injection at the time of TAI in P/AI (Control= 36.18% (169/467), GnRH= 45.95% (216/470); P<0.0001). In conclusion, GnRH application in cows with low HEATSC (1 and 2) is a simple strategy, requiring no changes in TAI management to increase pregnancy rates in postpartum beef cows submitted to progesterone-estradiol-based TAI protocols, without reaching, however, the pregnancy rates of cows that demonstrate high estrus expression at the TAI.

Kinin B2 receptor can play a neuroprotective role in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline, presence of amyloid-beta peptide (Aß) aggregates and neurofibrillary tangles. Kinins act through B1 and B2 G-protein coupled receptors (B1R and B2R). Chronic infusion of Aß peptide leads to memory impairment and increases in densities of both kinin receptors in memory processing areas. Similar memory impairment was observed in C57BL/6 mice (WTAß) but occurred earlier in mice lacking B2R (KOB2Aß) and was absent in mice lacking B1R (KOB1Aß). Thus, the aim of this study was to evaluate the participation of B1R and B2R in Aß peptide induced cognitive deficits through the evaluation of densitiesof kinin receptors, synapses, cell bodies and number of Aß deposits in brain ofWTAß, KOB1Aß and KOB2Aß mice. An increase in B2R density was observed in both WTAß and KOB1Aß in memory processing related areas. KOB1Aß showed a decrease in neuronal density and an increase in synaptic density and, in addition, an increase in Aß deposits in KOB2Aß was observed. In conclusion, memory preservation in KOB1Aß, could be due to the increase in densities of B2R, suggesting a neuroprotective role for B2R, reinforced by the increased number of Aß plaques in KOB2Aß. Our data point to B2R as a potential therapeutic target in AD.

Reduced LRP6 expression and increase in the interaction of GSK3ß with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea.

In diabetes mellitus (DM), podocyte apoptosis leads to albuminuria and nephropathy progression. Low-density lipoprotein receptor-related protein 6 (LRP6) is WNT pathway receptor that is involved in podocyte death, adhesion and motility. Glycogen synthase kinase 3 (GSK3) interaction with p53 (GSK3-p53) promotes apoptosis in carcinoma cells. It is unknown if GSK3-p53 contributes to podocyte apoptosis in DM. In experimental DM, green tea (GT) reduces albuminuria by an unknown mechanism. In the present study, we assessed the role of the GSK3ß-p53 in podocyte apoptosis and the effects of GT on these abnormalities. In diabetic spontaneously hypertensive rats (SHRs), GT prevents podocyte's p-LRP6 expression reduction, increased GSK3ß-p53 and high p53 levels. In diabetic SHR rats, GT reduces podocyte apoptosis, foot process effacement and albuminuria. In immortalized mouse podocytes (iMPs), high glucose (HG), silencing RNA (siRNA) or blocking LRP6 (DKK-1) reduced p-LRP6 expression, leading to high GSK3ß-p53, p53 expression, apoptosis and increased albumin influx. GSK3ß blockade by BIO reduced GSK3ß-p53 and podocyte apoptosis. In iMPs under HG, GT reduced apoptosis and the albumin influx by blocking GSK3ß-p53 following the rise in p-LRP6 expression. These effects of GT were prevented by LRP6 siRNA or DKK-1. In conclusion, in DM, WNT inhibition, via LRP6, increases GSK3ß-p53 and podocyte apoptosis. Maneuvers that inactivate GSK3ß-p53, such as GT, may be renoprotective in DM.

Associative memory deficits in mild cognitive impairment: the role of hippocampal formation.

Neuropathological events featuring early stages of Alzheimer's disease (AD) appear in the entorhinal cortex (EC), subiculum (SB) and cornu ammonis 1 (CA1) of hippocampus, which may account for associative memory deficits in non-demented people with mild cognitive impairment (MCI). To test this hypothesis in vivo, we investigated whether volume changes in these regions are related to failures in associative memory in MCI as compared to cognitively normal (CN) elderly subjects. Volume changes in EC and hippocampal subfields were determined by using deformation-based morphometry techniques applied to probabilistic cytoarchitectonic maps derived from post mortem human brains. CN subjects were distinguished from MCI patients by firstly identifying local volume differences in EC and hippocampus, and then evaluating the way in which these anatomical changes correlated with performance in a non-intentional face-location association task. MCI patients not only performed worse than CN elders in building new associations, but they were further unable to benefit from semantic encoding to improve episodic binding. According to our initial hypothesis, local volume reductions in both EC and hippocampal CA accounted for group differences in associative memory whereas atrophy in CA, but not in EC, accounted for semantic encoding of associations. Two main conclusions can be drawn from the present study: i) access to semantic information during encoding does not reduce the episodic deficit in MCI; and ii) EC and hippocampal CA, two regions early affected by AD neuropathology, are responsible, at least partially, for associative memory deficits observed in MCI patients.

Large-scale in vitro embryo production and pregnancy rates from Bos taurus, Bos indicus, and indicus-taurus dairy cows using sexed sperm.

Herein we describe a large-scale commercial program for in vitro production of embryos from dairy Bos taurus, Bos indicus, and indicus-taurus donors, using sexed sperm. From 5,407 OPU, we compared the number of recovered oocytes (n = 90,086), viable oocytes (n = 64,826), and embryos produced in vitro from Gir (Bos indicus, n = 617), Holstein (Bos taurus, n = 180), 1/4 Holstein × 3/4 Gir (n = 44), and 1/2 Holstein-Gir (n = 37) crossbred cows, and the pregnancy rate of recipient cows. Viable oocytes were in vitro matured (24 h at 38.8 °C, 5% CO(2) in air) and fertilized by incubating them for 18 to 20 h with frozen-thawed sexed sperm (X-chromosome bearing) from Gir (n = 8) or Holstein (n = 7) sires (2 × 10(6) sperm/dose). Embryos were cultured in similar conditions of temperature and atmosphere as for IVM, with variable intervals of culture (between Days 2 and 5) completed in a portable incubator. All embryos were transferred fresh, after 24 to 72 h of transportation (up to 2,000 km). On average, 16.7 ± 6.3 oocytes (mean ± SEM) were obtained per OPU procedure and 72.0% were considered viable. Total and viable oocytes per OPU procedure were 17.1 ± 4.5 and 12.1 ± 3.9 for Gir cows, 11.4 ± 3.9 and 8.0 ± 2.7 for Holstein cows, 20.4 ± 5.8 and 16.8 ± 5.0 for 1/4 Holstein × 3/4 Gir, and 31.4 ± 5.6 and 24.3 ± 4.7 for 1/2 Holstein-Gir crossbred females (P < 0.01). The mean number of embryos produced by OPU/IVF and the pregnancy rates were 3.2 (12,243/ 3,778) and 40% for Gir cows, 2.1 (2,426/1,138) and 36% for Holstein cows, 3.9 (1,033/267) and 37% for 1/4 Holstein × 3/4 Gir, and 5.5 (1,222/224), and 37% for 1/2 Holstein-Gir. In conclusion, we compared oocyte yield from two levels of indicus-taurus breeds and demonstrated the efficiency of sexed sperm for in vitro embryo production. Culturing embryos during long distance transportation was successful, with potential for international movement of embryos.

Human papillomavirus infection in Rio de Janeiro, Brazil: a retrospective study

There is considerable data to support a central role for human papillomavirus (HPV) in the etiology of cervical cancer. More than a 100 HPV types have been described, and 40 have been isolated from benign and malignant genital lesions. Consequently, there is strong motivation to evaluate HPV testing for cervical cancer screening. Few studies concerning the natural history of HPV infection have been conducted in the state of Rio de Janeiro. We determined the prevalence of HPV types in female genital lesions by using Hybrid Capture Assay (HCA) and we retrospectively analyzed the course of HPV infection. Our sample included 788 women attended at Laboratórios Sérgio Franco. The average age of the participants was 29.6 years. HPV prevalence and cytological diagnosis were determined. The overall prevalence of HPV DNA in the study group was 50.1 percent (395/788), ranging from 25 percent (NORMAL) to 100 percent in high-grade intraepithelial lesions (HSIL). High risk HPV was found in 12 percent inflammatory, 58.3 percent HPV, 63.2 percent LSIL and 100 percent HSIL. A retrospective analysis of 78 patients showed that 22 presented persistent lesions, 2 had progressive lesions, 4 had regressive lesions, 13 showed latent infections, 18 were transiently infected and 19 were submitted to curative treatment. No cases of cancer were registered in this population, which can afford private medical care and regular follow-up exams. We suggest that HCA be used in specific cases involving persistent and recurrent lesions.

Effects of different disinfection treatments on the natural microbiota of lettuce.

In this study, water and eight sanitizing solutions (vinegar at 6, 25, and 50%; acetic acid at 2 and 4%; peracetic acid at 80 ppm, sodium hypochlorite at 200 ppm, and sodium dichloroisocyanurate at 200 ppm) were compared in terms of their effectiveness against the natural microbiota of lettuce. All of the samples were kept in contact with the sanitizing solutions for 15 min, and the effectiveness of a sanitizing agent was evaluated on the basis of the number of decimal reductions of the total aerobic mesophilic count, the mold and yeast count, the total coliform count, and the Escherichia coli count. The average initial levels of these organisms in the samples were 6.94 log10 CFU/g for aerobic mesophilic microorganisms, 5.62 log10 CFU/g for molds and yeasts, and 3.25 log10 CFU/g for total coliforms. Of 10 samples analyzed, only 4 contained E. coli, and the average initial level of this microorganism in these 4 samples was 1.64 log10 CFU/g. Salmonella was not detected in any of the samples tested. The decimal reductions of the populations of aerobic mesophilic microorganisms, molds and yeasts, total coliforms, and E. coli were 0.78, 0.87, 0.82, and >0.14 log10 CFU/g, respectively, in water; 2.89, >3.41, >2.21, and >0.26 log10 CFU/g, respectively, in 50% vinegar; 2.42, >3.20, >1.99, and >0.26 log10 CFU/g, respectively, in 25% vinegar; 1.83, 2.57, 1.58, and >0.26 log10 CFU/g, respectively, in 6% vinegar; 3.91, >3.58, >2.25, and >0.26 log10 CFU/g, respectively, in 4% acetic acid; 3.37, >3.53, >2.25, and >0.26 log10 CFU/g, respectively, in 2% acetic acid; 1.85, 2.32, 1.44, and >0.20 log10 CFU/g, respectively, in 80 ppm of peracetic acid; 2.63, 2.75, 1.91, and >0.26 log10 CFU/g, respectively, in 200 ppm of sodium hypochlorite; and 3.23, >3.08, >1.95, and >0.26 log10 CFU/g, respectively, in 200 ppm of sodium dichloroisocyanurate. Statistical analysis of the results showed that the effectiveness levels for all of the sanitizing agents tested were equivalent to or higher than that for sodium hypochlorite at 200 ppm.

Bone age delay in Perthes disease and transient synovitis of the hip.

Patients with transient synovitis of the hip were found to have a bone age delay similar to the one found in patients in the active stages of Perthes disease. This finding led to a study on the relationship between the bone and chronologic ages in patients affected by either disease, in activity, and in the residual stage through to the end of growth. Bone age of all patients was established by means of a radiograph of both wrists and hands and the quantified data were compared with the Greulich and Pyle Atlas. All the patients in the active stage of both diseases revealed a bone age delay with different values and different time evolution but with some degree of overlapping between the thirtieth and seventieth months of age. The bone age delay persisted after healing of the respective disease and tended to diminish with time in an erratic way until the age of puberty when the bone and chronologic ages assume similar values. Transient synovitis of the hip usually occurs in only one hip.

Synthesis and analgesic activity of novel N-acylarylhydrazones and isosters, derived from natural safrole.

Anew series of antinociceptive compounds belonging to the N-acylarylhydrazone (NAH) class were synthesized from natural safrole (7). The most analgesic derivative represented by 10f, [(4'-N,N-dimethylaminobenzylidene-3-(3', 4'-methylenedioxyphenyl)propionylhydrazine], was more potent than dipyrone and indomethacin, used as standards. The NAH compounds described herein were structurally planned by molecular hybridization and classical bioisosterism strategies on previously reported analgesic NAH in order to identify the pharmacophoric contribution of the N-acylarylhydrazone moiety and investigate the structure-activity relationship (SAR) in these series.

Synthesis and pharmacological evaluation of new flosulide analogues, synthesized from natural safrole.

Four new aryl-sulfonamide derivatives (3a, 4a, 5a-b), having methylenedioxy group attached to phenyl ring, were prepared from natural safrole and evaluated as anti-inflammatory agents. The N-methylsulfonamide 3a and corresponding retrosulfonamide derivative 5a were more active than standards indomethacin and nimesulide, at the same molar concentration, in carrageenan-induced pleurisy assay.