The four pillars for treatment of heart failure with reduced ejection fraction (HFrEF) patients include angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin-receptor blocker (ARB)/angiotensin ...receptor-neprilysin inhibitor (ARNI), beta-blocker (BB), mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter-2 inhibitor (SGLT2i), unless contraindicated or not tolerated. They should be started or up titrated to maximally tolerated doses recommended in current guidelines. Despite proven benefits and strong guideline recommendations, their use and dosing in routine clinical practice have traditionally fallen below the levels achieved in clinical trials.
This analysis seeks to establish medication use and optimal dosage according to the clinical practice guidelines in HFrEF patients included in the RECOLFACA registry during recruitment and after six-month follow-up. Factors that limit its use could be identified in subsequent analysis.
The RECOLFACA registry was performed between 2017 and 2019. A descriptive analysis is performed considering the medication used in HFrEF patients (ACE-I/ARB/ARNI, BB, and/or MRA) and their dosage (<50%, 50-100% or 100% of the dosage recommended in guidelines) during recruitment and at 6-month follow-up. SGLT2i are not included in this analysis because were not available during this period.
The registry included 2528 patients, and this analysis included 1661 HFrEF patients from this registry. Among these patients 89.4%, 93.4% and 70.1% received ACE-I/ARB/ARNI, BB and ARM respectively during registry recruitment. At six-month follow-up, a decrease in its use was observed (57.9%, 53.3% and 44.2% respectively). Among patients with established medication during registry recruitment, only 10.4%, 16.5% and 4.7% received target doses of ACE-I/ARB/ARNI, BB or ARM respectively, which increased at six-month follow-up in ACE-I/ARB/ARNI and BB group (12.6% and 21.5% respectively) and decreased in ARM group (3.7%) (Figure 1). Less than 1% of patients were simultaneously receiving target doses of ACE-I/ARB/ARNI, BB and MRA during registry.
In HFrEF patients included in this registry, the use and dosage of the three groups of medications evaluated (ACEI/ARB/ARNI, BB and ARM) and that are recommended in current guidelines is low and more worrisome is that after time (6-month follow-up), this percentage is lower, as mentioned in other trials. There is minor increases in the number of patients reaching maximal doses of those therapies during follow-up. We need to continue working to be able to identify factors associated with low adherence, access to medication, and using maximal recommended/tolerated doses.
Culture conditions in shake flasks affect filamentous Streptomyces lividans morphology, as well the productivity and O-mannosylation of recombinant Ala-Pro-rich O-glycoprotein (known as the 45/47 kDa ...or APA antigen) from Mycobacterium tuberculosis. In order to scale up from previous reported shake flasks to bioreactor, data from the literature on the effect of agitation on morphology of Streptomyces strains were used to obtain gassed volumetric power input values that can be used to obtain a morphology of S. lividans in bioreactor similar to the morphology previously reported in coiled/baffled shake flasks by our group. Morphology of S. lividans was successfully scaled-up, obtaining similar mycelial sizes in both scales with diameters of 0.21 ± 0.09 mm in baffled and coiled shake flasks, and 0.15 ± 0.01 mm in the bioreactor. Moreover, the specific growth rate was successfully scaled up (0.09 ± 0.02 and 0.12 ± 0.01 h(-1), for bioreactors and flasks, respectively), and the recombinant protein productivity measured by densitometry, as well. More interestingly, the quality of the recombinant glycoprotein measured as the amount of mannoses attached to the C-terminal of APA was also scaled- up; with up to five mannose residues in cultures carried out in shake flasks; and six in the bioreactor. However, final biomass concentration was not similar, indicating that although the process can be scaled-up using the power input, others factors like oxygen transfer rate, tip speed or energy dissipation/circulation function can be an influence on bacterial metabolism.
Las malas condiciones nutricionales en muchas localidades mayas de Yucatán, México, persisten, a pesar de que se han implementado diversos programas. El objetivo fue comparar los efectos de una ...intervención nutricional basada en la comunidad con enfoque intercultural (INBC) y una intervención nutricional convencional (INC), sobre el índice de masa corporal (IMC) y la dieta en mujeres de localidades mayas de Yucatán. Fueron incluidas mujeres adultas con IMC ≥ 25kg/m2 de dos pequeñas localidades rurales mayas vecinas. Ambas intervenciones fueron de tres meses y con 11 sesiones, siguiendo la normatividad vigente; en la INBC fue utilizada la herramienta intercultural, denominada Plato del Bien Comer Maya, además se incluyeron en la INBC estrategias diseñadas con base en información obtenida en una fase previa de estudio cualitativo con entrevistas. El grupo con la INBC (n = 7), en comparación con el grupo con la INC (n = 9), tuvo una mayor disminución de IMC (-0,58 ± 0,70 kg/m2 y +0,27 ± 0,64 kg/m2; p = 0,042), de la circunferencia de cintura (-2,15 ± 2,60 cm y -0,50 ± 0,75 cm; p = 0,042) y del consumo de grasas (-53,23 ± 21,92 gramos y -7,34 ± 25,77 gramos; p = 0,004), así como mayor incremento en las frecuencias semanales de consumo de algunos alimentos locales como nance (p = 0,012), tamarindo (p = 0,001) y chile (p = 0,004), la INBC fue la única que presentó una disminución significativa en el consumo diario de calorías (basal: 2.067 ± 91 kcal/día, a los tres meses: 1.474 ± 31 kcal/día; p = 0,018), hubo en ambos grupos disminuciones en el consumo de alimentos ultraprocesados, pero sin diferencias comparando los grupos; el grupo con la INBC obtuvo mejores resultados que el grupo con la INC.
As más condições nutricionais em muitas localidades maias de Yucatán (México) persistem apesar da implementação de diversos programas. O objetivo era comparar os impactos de uma intervenção nutricional baseada na comunidade com enfoque intercultural (INBC) e uma intervenção nutricional convencional (INC), sobre o índice de massa corporal (IMC) e a dieta de mulheres de localidades maias de Yucatán. Foram incluídas mulheres adultas com IMC ≥ 25kg/m2 de duas pequenas localidades rurais maias vizinhas. Ambas as intervenções duraram três meses e contaram com 11 sessões, conforme as normas vigentes; na INBC, foi utilizada a ferramenta intercultural denominada Prato de Comer Bem Maia Plato del Bien Comer Maya, além de estratégias adicionais idealizadas com base em dados obtidos em uma fase prévia de estudo qualitativo com entrevistas. Em comparação com o grupo com a INC (n = 9), o grupo com a INBC (n = 7) teve maior diminuição de IMC (-0,58 ± 0,70 kg/m2 e +0,27 ± 0,64 kg/m2; p = 0,042), da circunferência abdominal (-2,15 ± 2,60 cm y -0,50 ± 0,75 cm; p = 0,042) e do consumo de gorduras (-53,23 ± 21,92 gramas y -7,34 ± 25,77 gramas; p = 0,004), bem como um aumento maior das frequências semanais de consumo de alguns alimentos locais como o murici (p = 0,012), o tamarindo (p = 0,001) e pimenta (p = 0,004). A INBC foi a única a apresentar uma diminuição significativa do consumo diário de calorias (inicial: 2.067 ± 91 kcal/dia, após três meses: 1.474 ± 31 kcal/dia; p = 0.018). Houve em ambos os grupos redução equivalente do consumo de alimentos ultraprocessados; o grupo com a INBC obteve melhores resultados que o grupo com a INC.
Poor nutritional conditions persist in many Mayan communities in Yucatán, Mexico, even though various programs have been implemented. The study aimed to compare the effects of a community-based nutritional intervention with an intercultural focus versus a conventional nutritional intervention on body mass index (BMI) and diet in women in Mayan communities in Yucatán. The sample included adult women with BMI ≥ 25kg/m2 from neighboring rural Mayan villages. Both interventions lasted three months with 11 sessions and followed the prevailing guidelines. The community-based intervention used an intercultural tool called Good Mayan Food Plato del Bien Comer Maya, besides strategies designed according to information obtained from a prior qualitative study phase using interviews. The group that received the community-based intervention (n = 7), compared to the conventional intervention group (n = 9), showed larger decreases in BMI (-0.58 ± 0.70 kg/m2 and +0.27 ± 0.64kg/m2; p = 0.042), waist circumference (-2.15 ± 2.60 cm and -0.50 ± 0.75 cm; p = 0.042), and consumption of fats (-53.23 ± 21.92 grams and -7.34 ± 25.77 grams; p = 0.004), as well as higher increases in weekly consumption of some local foods such as nance fruit (p = 0.012), tamarind (p = 0.001), and chili peppers (p = 0.004). The community-based intervention was the only one to show a significant decrease in daily calorie intake (baseline: 2,067 ± 91 kcal/day, at three months: 1,474 ± 31 kcal/day; p = 0.018), and both groups showed decreases in the consumption of ultra-processed foods, but without significant differences between the two groups. The community-based intervention group showed better results than the conventional intervention group.
There are few published real-world studies on hepatitis C in Latin America. This paper describes a cohort of Colombian subjects treated with direct-acting antiviral agents. A total of 195 patients ...from 5 hepatology centers in 4 Colombian cities were retrospectively studied. For each patient, serum biomarkers were obtained, and Child-Pugh, MELD, cirrhosis and fibrosis stage were calculated. Additionally, viral load was quantified at initiation, end of treatment and at 12 weeks of completion. Adverse effects were recorded. Patients with liver transplant were compared with non-transplanted patients in terms of serum biomarkers. The patients had received 9 different regimes. The most prevalent viral genotype was 1b (81.5%). Overall, 186 patients (95.4%) attained sustained virologic response. When comparing transplanted vs. non-transplanted patients, those in the non-transplanted group were more likely to have cirrhosis (52.6% vs. 12.5%, p = 0.0004). Pre-treatment viral load was higher in the transplant group (1 743 575 IQR = 1 038 062-4 252 719 vs. 345 769 IQR = 125 806-842 239; p < 0.0001) as well as ALT and AST levels (82.5 IQR 43.5-115.5 vs. 37.0 IQR = 24.7-73.3; p = 0.0009 and 70 IQR = 41-140 vs. 37 IQR = 24-68; p = 0.004 respectively). Adverse events were reported by 28.7% of the patients; asthenia (5.6%) was the most prevalent. Our results are comparable with those from other countries in terms of therapy and biomarkers. However, our cohort reported less adverse events. Further research is needed in the region.
Rice is susceptible to cold during early developmental stages. Most tolerant cultivars have been developed for other conditions than those occurring in South America’s rice growing areas, or their ...grain type is not suitable for the local markets. If locally adapted varieties were available, growers could anticipate sowing date, making flowering time coincide with the moment of maximum solar radiation and increasing yields. In this work, 116 rice inbred lines and varieties of diverse origin within the South American gene pool were tested for seedling survival and germination percentage under low temperature in controlled conditions. As a result, lines used as controls responded as expected, whereas lines with similar behavior to controls, intermediate between susceptible and tolerant controls and more extreme than controls were detected at both seedling and germination stages. Allelic variation at candidate genes OsGSTZ1, OsGSTZ2 and OsCDPK13 was analyzed in a subset of ten contrasting lines. Ten out of thirty-four polymorphisms detected in all three genes were associated with cold tolerance in these lines. A functional marker, designed from an aminoacid-changing SNP found in gene OsGSTZ2, was tested in the 116 lines. As a result, a tight association was observed between cold tolerance and marker score. In conclusion, wide variability for cold tolerance at early developmental stages has been detected in rice advanced breeding materials that are adapted to local growing conditions. Also, a functional marker tightly associated with the trait is available for performing marker assisted selection.
Obesity and its comorbidities are increasingly prevalent in Latin America, with a more rapid growth in individuals with lower income. The composition of movement behaviors within a 24 h period may ...have important implications for obesity, metabolic and mental health in cross-sectional data. However, a longitudinal study is needed to confirm the findings from the primarily cross-sectional evidence. The COVID-19 pandemic has been associated with cardiometabolic outcomes and has impeded healthy behavior.
The first objective is to evaluate the time elapsed since the diagnosis of not meeting 24 h movement guidelines and the potential subsequent onset of metabolic syndrome in undergraduate students from low-income regions within 4 years of follow up. The second objective is to test the association between 24 h movement, mental wellbeing, eating behaviors, and abdominal obesity in the period of this pandemic.
The 24 h movement behavior and metabolic syndrome (24 h-MESYN) study is a multicentre cohort study that will include participants from two Brazilian cities within the 2022-2025 period to asses the first objective, and also a nested case-control study at the baseline will be carried out to evaluate the second objective. Previously, we conducted a feasibility study in the academic year of 2021 to assessing the psychometric properties of subjective tools, refine our study protocol, and adjust the epidemiological conditions of the cohort's subsequent phases (like as prevalence of exposure of interest, sampling process, and study adherence). Statistical tests as Cohen's kappa agreement; factorial analysis; logistic, Poisson and linear regression; and Kaplan-Meier analysis will be performed, in accordance with the objectives.
Alteration of vitamin B
metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early ...diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B
deficiency have been detected by clinical symptoms and only few of them trough NBS programs. We aim to assess the usefulness of the second-tier test: methylmalonic acid (MMA), methylcitric acid (MCA) and homocysteine (Hcys) in our newborn screening program and explore the implications on the detection of cobalamin (vitamin B
) related disorders, both genetic and acquired conditions.
A screening strategy using the usual primary markers followed by the analysis of MMA, MCA and Hcys as second tier-test in the first dried blood spot (DBS) was developed and evaluated.
During the period 2015-2018 a total of 258,637 newborns were screened resulting in 130 newborns with acquired vitamin B
deficiency (incidence 1:1989), 19 with genetic disorders (incidence 1:13,613) and 13 were false positive. No false negatives were notified. Concerning the second-tier test, the percentage of cases with MMA above the cut-off levels, both for genetic and acquired conditions was very similar (58% and 60%, respectively). Interestingly, the percentage of cases with increased levels of Hcys was higher in acquired conditions than in genetic disorders (87% and 47%, respectively). In contrast, MCA was high only in 5% of the acquired conditions versus in 53% of the genetic disorders, and it was always very high in all patients with propionic acidemia.
When screening for methylmalonic acidemia and homocystinuria, differential diagnosis with acquired vitamin B
deficiency should be done. The results of our strategy support the inclusion of this acquired condition in the NBS programs, as it is easily detectable and allows the adoption of corrective measures to avoid the consequences of its deficiency.
We aimed to compare the effect of three estradiol benzoate (EB) doses on follicular wave emergence (FWE) and dominant follicle growth of suckled Nelore cows submitted to TAI (D0). On a random day of ...estrous cycle (D−10), multiparous (MULT; n=36) and primiparous (PRIM; n=20) suckled Nelore cows received an intravaginal progesterone (P4) device and were assigned in three groups. Cows in the EB-1 (n=20), EB-1.5 (n=15) or EB-2 (n=21) groups received, respectively, an im treatment with 1, 1.5 or 2 mg EB. A subgroup (n=10-13 cows/group) were subject to daily ovarian evaluations from D−10 to D0. On D−2, P4 devices were removed, and all cows received the same treatment: 1 mg estradiol cypionate, 0.53 mg sodium cloprostenol, and 300 IU eCG. Statistical analyses were performed considering only the main effects of treatment group and parity order. The proportion of cows with a synchronized FWE and the moment of the FWE did not differ (
p
>0.05) among the treatment groups (overall: 80% 28/35 and 4.1 ± 0.4 days); however, the FWE occurred earlier (
p
=0.007) in MULT (3.8 ± 0.2 days) than PRIM (5.1 ± 0.4) cows. The proportion of animals detected in estrus was greater (86% 31/36
vs.
70% 14/20;
p
=0.02) and the dominant follicle was larger on D−2 (9.7 ± 0.3 mm
vs.
7.8 ± 0.7 mm;
p
=0.006) and D0 (11.9 ± 0.4 mm
vs.
10 ± 0.5 mm;
p
=0.008) in MULT than PRIM cows. In conclusion, the three EB doses presented similar efficiency to synchronize the FWE in suckled Nelore cows. Moreover, a delayed FWE and smaller dominant follicle is observed in PRIM cows, contributing to the reduced reproductive performance in this parity category when using similar TAI protocols of MULT cows.
We aimed to elucidate whether NO acts in in vitro sperm capacitation in bovine via cGMP/PKG1 pathway. For this, cryopreserved bovine sperm were capacitated in vitro with 20 µg/ml heparin (Control) ...plus treatments: 1 mM L‐arginine (L‐arg, NO precursor), 50 µM Rp‐8‐Bromo‐β‐phenyl‐1,N2‐ethenoguanosine‐3′,5′‐cyclic monophosphorothioate (Rp‐8‐Br‐cGMPS, selective inhibitor of the binding site for cGMP in PKG1), 1 mM 2‐Phenyl‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl 3‐oxide (PTIO, NO scavenger), and the combinations of L‐arg + RP‐8‐Br‐cGMPS and L‐arg + PTIO. Sperm motility and vigour were determined by phase‐contrast microscopy, capacitation status by chlortetracycline staining, and the intracellular concentration of cGMP was measured by ELISA. Data were subjected to analysis of variance and means compared with SNK test at 5% probability. Motility and vigour were lower in sperm treated with PTIO when compared to Control and other treatments (p < .05). The L‐arg treatment showed the highest percentage of capacitated sperm when compared to the Control and other treatments (Rp‐8‐Br‐cGMPS, L‐arg + Rp‐8‐Br‐cGMPS and PTIO) (69.8 ± 3.4%, 51.2 ± 3.0, 51.1 ± 2.1, 51.2 ± 3.0 and 45.5 ± 2.7, respectively) (p < .05). The capacitation ratio (%) was lower in treatments with Rp‐8‐Br‐cGMPS, L‐arg + Rp‐8‐Br‐cGMPS and PTIO, respectively (p < .05). Lastly, cGMP concentration (pmol/ml) was lower in PTIO and L‐arg + PTIO (1.3 ± 0.3 and 1.6 ± 0.4) and was higher in Rp‐8‐Br‐cGMPS and L‐arg + Rp‐8‐Br‐cGMPS (3.7 ± 0.4 and 4.0 ± 0.5) treatments. We showed that during in vitro capacitation of cattle: (a) NO influences sperm motility and vigour; (b) NO is associated with cGMP synthesis through two independent pathways and (c) the cGMP/PKG1 pathway has a partial role in sperm capacitation and does not involve the L‐arg/NO.
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