Cryptococcal infections are mainly caused by members of the Cryptococcus neoformans species complex (molecular types VNI, VNII, VNB, VNIV and the AD hybrid VNIII). PCR of the mating type loci and ...MLST typing using the ISHAM-MLST consensus scheme were used to evaluate the genetic relationship of 102 (63 clinical and 39 environmental) C. neoformans isolates from Uberaba, Brazil and to correlate the obtained genotypes with clinical, antifungal susceptibility and virulence factor data. All isolates were mating type alpha. MLST identified 12 known and five new sequence types (ST). Fourteen STs were identified within the VNI isolates, with ST93 (57/102, 56%) and ST77 (19/102, 19%) being the most prevalent. From the nine VNII isolates previously identify by URA5-RFLP only four (ST40) were confirmed by MLST. The remaining five grouped within the VNB clade in the phylogenetic analysis corresponding to the sequence type ST504. Other two environmental isolates also grouped within VNB clade with the new sequence type ST527. The four VNII/ST40 isolates were isolated from CSF. The two VNIV sequence types (ST11 and ST160) were isolated from blood cultures. Two of six patients evaluated with more than one isolates had mixed infections. Amongst the VNI isolates 4 populations were identified, which showed differences in their susceptibility profiles, clinical outcome and virulence factors. These results reinforce that ST93 is the most prevalent ST in HIV-infected patients in the Southeastern region of Brazil. The finding of the VNB molecular type amongst environmental Brazilian isolates highlights that this genotype is not restricted to the African continent.
The organisation and systematisation of health actions and services are essential to ensure patient safety and the effectiveness and efficiency of cancer care. The objective of this study was to ...analyse the structure of cancer care envisaged in Brazilian norms, describe the types of accreditations of cancer services and their geographic distribution, and determine the planning and evaluation parameters used to qualify the health units that provide cancer care in Brazil.
This observational study identified the current organisation of cancer care and other health services that are accredited by Brazil's national health system (SUS) for cancer treatment as of February 2017. The following information was collected from the current norms and the National Registry of Health Establishments: geographic location, type of accreditation, type of care, and hospital classification according to annual data of the number of cancer surgeries. The adequacy of the number of licensed units relative to population size was assessed. The analysis considered the facilitative or restrictive nature of policies based on the available rules and resources.
The analysis of the norms indicated that these documents serve as structuring rules and resources for developing and implementing cancer care policies in Brazil. A total of 299 high-complexity oncology services were identified in facilities located in 173 (3.1%) municipalities. In some states, there were no authorised services in radiotherapy, paediatric oncology and/or haematology-oncology. There was a significant deficit in accredited oncology services.
The parameters that have been used to assess the need for accredited cancer services in Brazil are widely questioned because the best basis of calculation is the incidence of cancer or disease burden rather than population size. The results indicate that the availability of cancer services is insufficient and the organisation of the cancer care network needs to be improved in Brazil.
Introduction. Acute-on-chronic liver failure (ACLF) is an acute liver decompensation in cirrhotic patients, which leads to organ failures and high short-term mortality. The treatment is based on the ...management of complications and, in severe cases, liver transplantation. Since specific treatment is unavailable, we aimed to evaluate the safety and initial efficacy of bone marrow mesenchymal stem cells (BM-MSC) in patients with ACLF Grades 2 and 3, a population excluded from previous clinical trials. Methods. This is a randomized placebo-controlled phase I-II single center study, which enrolled 9 cirrhotic patients from 2018 to 2020, regardless of the etiology. The control group (n = 5) was treated with standard medical therapy (SMT) and placebo infusion of saline. The intervention group (n = 4) received SMT plus 5 infusions of 1 × 106 cells/kg of BM-MSC for 3 weeks. Both groups were monitored for 90 days. A Chi-square test was used for qualitative variables, and the t-test and Mann–Whitney U test for quantitative variables. The Kaplan–Meier estimator was used to build survival curves. In this study, we followed the intention-to-treat analysis, with a significance of 5%. Results. Nine patients with a mean Child–Pugh (CP) of 12.3, MELD of 38.4, and CLIF-C score of 50.7 were recruited. Hepatitis C and alcohol were the main etiologies. The average infusion per patient was 2.9 and only 3 patients (2 in control and 1 in the BM-MSC group) received all the protocol infusions. There were no infusion-related side effects, although one patient in the intervention group presented hypernatremia and a gastric ulcer, after the third and fifth infusions, respectively. The survival rate after 90 days was 20% (1/5) for placebo versus 25% (1/4) for the BM-MSC. The patient who completed the entire MSC protocol showed a significant improvement in CP (C-14 to B-9), MELD (32 to 22), and ACLF (grade 3 to 0). Conclusion. BM-MSC infusion is safe and feasible in patients with ACLF Grades 2 and 3.
In the above article <xref ref-type="bibr" rid="ref1">1 , the funding was incorrectly listed. The correct funding statement should be: "This work was supported by Fundação para a Ciência e Tecnologia ...(FCT) and Instituto de Telecomunicações under projects UID/EEA/50008/2019, PES3N (LISBOA- 01-0145-FEDER-030629), and MASSIVE5G (SAICT-45-2017-02)."
This research proposes a new variant of Nowak and Sigmund’s indirect reciprocity model focused on agents’ individualism, which means that an agent strengthens its profile to the extent to which it ...makes a profit; this is using agent-based modeling. In addition, our model includes environmentally related conditions such as visibility and cooperative demand and internal poses such as obstinacy. The simulation results show that cooperators appear in a more significant proportion with conditions of low reputation visibility and high cooperative demand. Still, severe defectors take advantage of this situation and exceed the cooperators’ ratio. Some events show a heterogeneous society only with conditions of high obstinacy and cooperative demand. In general, the simulations show diverse scenarios, including centralized, polarized, and mixed societies. Simulation results show no healthy cooperation in indirect reciprocity due to individualism.
Objectives
To evaluate the inter-rater agreement of chest X-ray (CXR) findings in coronavirus disease 2019 (COVID-19) and to determine the value of initial CXR along with demographic, clinical, and ...laboratory data at emergency department (ED) presentation for predicting mortality and the need for ventilatory support.
Methods
A total of 340 COVID-19 patients who underwent CXR in the ED setting (March 1–13, 2020) were retrospectively included. Two reviewers independently assessed CXR abnormalities, including ground-glass opacities (GGOs) and consolidation. Two scoring systems (
Brixia
score and percentage of lung involvement) were applied. Inter-rater agreement was assessed by weighted Cohen’s kappa (
κ
) or intraclass correlation coefficient (ICC). Predictors of death and respiratory support were identified by logistic or Poisson regression.
Results
GGO admixed with consolidation (
n
= 235, 69%) was the most common CXR finding. The inter-rater agreement was almost perfect for type of parenchymal opacity (
κ
= 0.90),
Brixia
score (ICC = 0.91), and percentage of lung involvement (ICC = 0.95). The
Brixia
score (OR: 1.19; 95% CI: 1.06, 1.34;
p
= 0.003), age (OR: 1.16; 95% CI: 1.11, 1.22;
p
< 0.001), PaO
2
/FiO
2
ratio (OR: 0.99; 95% CI: 0.98, 1;
p
= 0.002), and cardiovascular diseases (OR: 3.21; 95% CI: 1.28, 8.39;
p
= 0.014) predicted death. Percentage of lung involvement (OR: 1.02; 95% CI: 1.01, 1.03;
p
= 0.001) and PaO
2
/FiO
2
ratio (OR: 0.99; 95% CI: 0.99, 1.00;
p
< 0.001) were significant predictors of the need for ventilatory support.
Conclusions
CXR is a reproducible tool for assessing COVID-19 and integrates with patient history, PaO
2
/FiO
2
ratio, and SpO
2
values to early predict mortality and the need for ventilatory support.
Key Points
• Chest X-ray is a reproducible tool for assessing COVID-19 pneumonia.
•
The Brixia score and percentage of lung involvement on chest X-ray integrate with patient history, PaO
2
/FIO
2
ratio, and SpO
2
values to early predict mortality and the need for ventilatory support in COVID-19 patients presenting to the emergency department.
Comorbidities and comedication are common in patients with hepatitis C, which could result in a risk of drug-drug interaction. The objective of this study was to evaluate the prevalence of ...comorbidities, comedication and drug-drug interactions involving direct-acting antivirals in this population.
Comorbidities and comedications were evaluated in a retrospective cohort of hepatitis C patients. Drug-drug interactions were estimated in real life and with simulated data on comedications following drug regimens: telaprevir; elbasvir/grazoprevir, ombitasvir/paritaprevir/r/ritonavir (2D regimen), and sofosbuvir/simeprevir, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir; 2D/dasabuvir (3D regimen); glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir. The interactions were evaluated according to the University of Liverpool database. Statistical analysis was performed by SPSS® 18.0.
Data from 1433 patients with hepatitis C were evaluated. The mean patient age was 51.7 years (SD ± 10.7), and 50.6% were female. Direct-acting antivirals were prescribed for 345 (24.1%) patients, and a sustained virological response occurred in 264 (76.5%). The main comorbidities were systemic arterial hypertension 436 (30.4%), diabetes mellitus 352 (24.6%) and depression 130 (9.1%). The mean number of comorbidities was 1.52 (median IQR of 1.00 1.00-2.00). The mean number of comedications was 3.16 (median IQR of 3.00 1.00-5.00). A total of 12916 drug-drug interactions were found, of which 1.859 (14.4%) were high risk, with a mean of 1.29 ± 3.13 per patient. The 3D regimen, as well as glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir, presented the highest drug-drug interaction indexes.
Comorbidities and comedications are common in patients with hepatitis C, as are drug-drug interactions. Even when second generation drugs are used, the occurrence of drug-drug interactions still presents a significant risk.
Entomological surveillance is a traditional method to measure presence, distribution, and seasonal variation of vectors in urban areas, and is essential to targeted control activities to prevent ...arbovirus transmission. Ovitraps as one of the main components of surveillance programs, enable determination of female oviposition behavior, as well as identification of seasonal variations of the vector. The goals of this study were 1) to detect the mosquitos (Aedes aegypti Linnaeus) and (Aedes albopictus Skuse) (Diptera:Culicidae), in Paranaguá city, 2) to assess ovitrap positive index (OPI), egg density index (EDI), and their relationship with meteorological variables, and 3) to evaluate the vertical transmission of dengue, Zika, and chikungunya in Ae. aegypti and Ae. albopictus. The study was carried out in urban areas of Paranaguá city, an important port region of Brazil, from June 2017 to November 2018. The city was divided into 16 area-clusters. Three-hundred and thirty-one ovitraps were installed monthly, remaining for four days in selected places. Kernel density maps were done to compare the spatiotemporal distribution of collected eggs. Areas which maintained constant oviposition associated with vector activity were identified and were found to overlap the area-clusters with the highest EDI. As viral RNA was not detected, vertical transmission was likely not a maintenance mechanism of arbovirus circulation in Ae. aegypti and Ae. albopictus vectors. This study reiterates the importance, efficiency, and feasibility of ovitraps to monitor the presence and dynamics of Aedes spp. populations.
The cardiac circadian clock is responsible for the modulation of different myocardial processes, and its dysregulation has been linked to disease development. How this clock machinery is regulated in ...the heart remains an open question. Because noradrenaline (NE) can act as a zeitgeber in cardiomyocytes, we tested the hypothesis that adrenergic signaling resets cardiac clock gene expression in vivo. In its anti‐phase with Clock and Bmal1, cardiac Per1 abundance increased during the dark phase, concurrent with the rise in heart rate and preceded by an increase in NE levels. Sympathetic denervation altered Bmal1 and Clock amplitude, while Per1 was affected in both amplitude and oscillatory pattern. We next treated mice with a β‐adrenergic receptor (β‐AR) blocker. Strikingly, the β‐AR blockade during the day suppressed the nocturnal increase in Per1 mRNA, without altering Clock or Bmal1. In contrast, activating β‐AR with isoproterenol (ISO) promoted an increase in Per1 expression, demonstrating its responsiveness to adrenergic input. Inhibitors of ERK1/2 and CREB attenuated ISO‐induced Per1 expression. Upstream of ERK1/2, PI3Kγ mediated ISO induction of Per1 transcription, while activation of β2‐AR, but not β1‐AR induced increases in ERK1/2 phosphorylation and Per1 expression. Consistent with the β2‐induction of Per1 mRNA, ISO failed to activate ERK1/2 and elevate Per1 in the heart of β2‐AR−/− mice, whereas a β2‐AR antagonist attenuated the nocturnal rise in Per1 expression. Our study established a link between NE/β2‐AR signaling and Per1 oscillation via the PI3Ky‐ERK1/2‐CREB pathway, providing a new framework for understanding the physiological mechanism involved in resetting cardiac clock genes.
The aim of this article is to study the conventional and cooperative power-order Non-Orthogonal Multiple Access (NOMA) using the Single Carrier with Frequency Domain Equalization (SC-FDE) block ...transmission technique, associated with massive Multiple-Input Multiple-Output (MIMO), evidencing its added value in terms of spectral efficiency of such combined scheme. The new services provided by Fifth Generation of Cellular Communications (5G) are supported by new techniques, such as millimeter waves (mm-wave), alongside the conventional centimeter waves and by massive MIMO (m-MIMO) technology. NOMA is expected to be incorporated in future releases of 5G, as it tends to achieve a capacity gain, highly required for the massive number of Internet of things (IoT) devices, namely to support an efficient reuse of limited spectrum. This article shows that the combination of conventional and cooperative NOMA with m-MIMO and SC-FDE, tends to achieve capacity gains, while the performance only suffers a moderate degradation, being an acceptable alternative for future evolutions of 5G. Moreover, it is shown that Cooperative NOMA tends to outperform Conventional NOMA. Moreover, this article shows that the Maximum Ratio Combiner (MRC) receiver is very well fitted to be combined with NOMA and m-MIMO, as it achieves a good performance while reducing the receiver complexity.
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