IMPORTANCE: It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in ...patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). INTERVENTIONS: Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. MAIN OUTCOMES AND MEASURES: The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. RESULTS: Among 659 patients, the median age was 55.1 years (interquartile range IQR, 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days SD, 8 days) vs patients in the continuation group (mean, 22.9 days SD, 7.1 days) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio OR, 0.97 95% CI, 0.38-2.52), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 95% CI, 0.19-42.12), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 95% CI, 0.95-1.80). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04364893
Zika virus (ZIKV) infection has been associated with severe complications both in the developing and adult nervous system. To investigate the deleterious effects of ZIKV infection, we used human ...neural progenitor cells (NPC), derived from induced pluripotent stem cells (iPSC). We found that NPC are highly susceptible to ZIKV and the infection results in cell death. ZIKV infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. Induction of apoptosis of Sox2
cells was demonstrated by activation of caspases 3/7, 8 and 9, and by ultrastructural and flow cytometry analyses. ZIKV-induced death of Sox2
cells was prevented by incubation with the pan-caspase inhibitor, Z-VAD-FMK. By confocal microscopy analysis we found an increased number of cells with supernumerary centrosomes. Live imaging showed a significant increase in mitosis abnormalities, including multipolar spindle, chromosome laggards, micronuclei and death of progeny after cell division. FISH analysis for chromosomes 12 and 17 showed increased frequency of aneuploidy, such as monosomy, trisomy and polyploidy. Our study reinforces the link between ZIKV and abnormalities in the developing human brain, including microcephaly.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying ...mechanism has not been fully elucidated.
Methods
All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury.
Results
The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8
+
CD38
+
mean fluorescence intensity (MFI), and percentage of CD8
+
human leukocyte antigen DR isotope (HLA-DR)
+
CD38
–
cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)
+
MFI, percentage of CD8
+
CD38
+
cells, CD8
+
HLA-DR
+
MFI, CD8
+
NKG2A
+
MFI, and percentage of CD8
+
HLA-DR
–
CD38
+
cells. On multivariate regression, the CD8
+
HLA-DR
+
MFI, CD8
+
CD38
+
MFI, and total lymphocyte count were associated significantly with myocardial injury.
Conclusion
Our findings suggest that lymphopenia, CD8
+
CD38
+
MFI, and CD8
+
HLA-DR
+
MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Endovascular thrombectomy has been effective in reducing stroke-related disability in high-income countries. This trial in the public health care system of Brazil, a developing country, showed ...similar effectiveness in patients treated within 8 hours after the onset of symptoms.
The kallikrein-kinin system has been implicated in body weight and glucose homeostasis. Their major effectors act by binding to the kinin B2 and B1 receptors. It was assessed the role of the kinin B1 ...receptor in weight and glucose homeostasis in B1 receptor knockout mice (B1RKO) subjected to a cafeteria diet (CAF). Wild-type (WT) and B1RKO male mice (C57BL/6 background; 8 weeks old) were fed a standard diet (SD) or CAF for 14 weeks, ad libitum, and four groups were formed: WT-SD; B1RKO-SD; WT-CAF; B1RKO-CAF. Body weight and food intake were assessed weekly. It was performed glucose tolerance (GTT) and insulin tolerance tests (ITT), and HOMA-IR, HOMA-β and HOMA-β* 1/HOMA-IR were calculated. Islets from WT and B1RKO were isolated in order to measure the insulin secretion. Western blot was used to assess the hepatic AKT phosphorylation and qPCR to assess gene expression. CAF induced a higher body mass gain in B1RKO compared to WT mice. CAF diet increased epididymal fat depot mass, hepatic fat infiltration and hepatic AKT phosphorylation in both genotypes. However, B1RKO mice presented lower glycemic response during GTT when fed with CAF, and a lower glucose decrease in the ITT. This higher resistance was overcomed with higher insulin secretion when stimulated by high glucose, resulting in higher glucose uptake in the GTT when submitted to CAF, despite lower insulin sensitivity. Islets from B1RKO delivered 4 times more insulin in 3-month-old mice than islets from WT. The higher insulin disposition index and high insulin delivery of B1RKO can explain the decreased glucose excursion during GTT. In conclusion, CAF increased the β-cell function in B1RKO mice, compensated by the diet-induced insulin resistance and resulting in a healthier glycemic response despite the higher weight gain.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The current study aims to determine the rhythmicity pattern in ammonia level inside broiler chicken houses raised on a traditional deep litter system. A total of 182 Ross broiler chickens (91 in the ...summer and 91 in the winter). Rice straw was used under three conditions: new, reused, and reused with daily wetting. Three daily readings of NH
3
were performed at two heights during a 42-day cycle. The data were tabulated, normalized, and expressed in terms of ppm/°C/bird. Fisher's statistical test was used to determine differences related to reading point, temperature, and moisture. The Hurst coefficient was determined in the occurrence of rhythmicity in the temporal variation and the COSINOR method was employed for the determination of patterns of rhythmic variation in NH
3
level. Fisher's method was employed to determine the descriptive capacity of the equations, considering a p-value of <0.01 as indicative of a statistically significant difference. Rhythmic variation in NH
3
level was found during the 42-day raising cycle and increased slightly in the winter. However, the different conditions of litter did not influence on ammonia level. These findings can assist in adaptations to broiler chicken management, providing a safer environment.
Full text
Available for:
BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
To meet the global demand for animal protein, sustainable intensification of existing livestock systems may be possible, especially through integration of livestock with crops or forestry. Thus, our ...objective was to compare forage production and animal performance in grass monoculture and integrated systems in the Brazilian Amazon biome. The four systems were (a) livestock (L) with Marandu palisadegrass {Brachiaria brizantha (Hochst. ex A. Rich.) R. D. Webster} as monoculture, (b) palisadegrass pastures integrated with eucalyptus trees (Eucalyptus urograndis; hybrid of Eucalyptus grandis W. Hill ex Maiden and Eucalyptus urophylla S. T. Blake) arranged in three‐row groves with groves spaced 30 m apart (livestock–forestry; LF), (c) palisadegrass after two years of crops (crop–livestock; CL) and (d) palisadegrass after two years of crops with single rows of eucalyptus trees spaced 37 m apart (crop–livestock–forestry; CLF). From July 2016 to July 2017, all experimental units were continuously stocked using a variable stocking rate. Greater herbage accumulation (HA) occurred in CL and CLF in comparison with L and LF (21,310, 24,050, 19,500 and 18,890 kg DM/ha respectively). The gain per hectare of L, LF and CL (average of 932 kg ha–1) was less than CLF (1,190 kg ha–1). Average daily gain was similar among systems (0.69 kg/day). We conclude that integrated systems can support similar (LF or CL) or greater (CLF) levels of animal production than palisadegrass monocultures while increasing diversity of outputs, thereby providing a greater range of viable systems for livestock production in the Brazilian Amazon biome.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
Children with meningomyelocele may require continuous care. Consequently, there is a risk for caregiver burden and impact on family quality of life (QoL), including siblings' QoL. Some ...studies analysed caregivers' burden and family QoL separately. However, none of these studies evaluated siblings' QoL and the associations between these three dimensions. This study investigated the associations between caregivers' burden, family QoL and siblings' QoL in Brazilian families of children with meningomyelocele and its correlations with sociodemographic, functional and clinical variables. Siblings' QoL was specifically assessed using as a parameter the QoL of typically developed Brazilian children.
Methods
One hundred and fifty families, 150 caregivers and 68 siblings completed the Family Quality of Life Scale, Burden Interview, KIDSCREEN‐27 Child and Adolescent Version and Parents Version questionnaires.
Results
Most families and caregivers reported a high family QoL and a low caregiver burden. Family QoL was significantly lower as caregivers' burden increased. Caregiver's burden was significantly lower with increasing family QoL levels. Self‐reported siblings' QoL was significantly worse than that of typically developed peers. There were no significant differences between self and parent‐reported siblings' QoL. Self‐reported siblings' QoL was significantly worse as their age increased and better with increasing family QoL levels. Parent‐reported siblings' QoL was significantly worse with increasing levels of caregiver's burden and significantly better as family QoL increased. There were no significant associations with functional and clinical variables.
Conclusions
Despite the cross‐sectional nature of the available data precludes any statements of causality, our results reinforce the relevance of knowing the factors that influence the QoL of families and siblings of children and adolescents with meningomyelocele and the relevance of actions aimed at reducing caregivers' burden, improving family QoL and meeting siblings' individual needs. Future multicenter studies may validate the generalizability of our findings.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We report the relevance of cation–anion and cation–solvent–anion interactions to the crystal lattice rigidity and the corresponding effect on the SCO behaviour of six Fe III complexes with the ...hexadentate Schiff base ligand nsal 2 trien. Four of these compounds were synthesized and structurally and magnetically characterized for the first time. In the most rigid structures, the SCO behaviour is either not allowed or severely hampered. For lower structural connectivity, incomplete transitions are observed within the 4–300 K temperature range. The most flexible structure shows a complete transition. The interactions between the cationic units and the anions were found to be more important than the cation–cation interactions for the SCO phenomenon and for the overall cooperativity related to the abrupt/gradual character of the transition. Computational studies were performed in order to determine the crystal splitting gap Δ oct . The calculated values for the HS and LS Δ oct are very similar for all compounds suggesting that these parameters have very little influence on the SCO behaviour.
PDF
