Neuropsychological manifestations of long COVID in hospitalized and non-hospitalized Brazilian Patients.

BACKGROUND: There has been a significant increase in number of patients seeking neuropsychological rehabilitation months after the acute phase of COVID-19 infection. OBJECTIVE: Identify the cognitive and psychiatric disorders in patients with long COVID or Post-Acute Sequelae of COVID (PASC) and explore the association between disease severity during the acute phase and persistent neuropsychological manifestations. METHODS: 614 adults were assessed an average of eight months post-infection. Participants were, on average, 47.6 y.o., who sought rehabilitation for neuropsychological problems. Patients were evaluated using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), Phonemic Verbal Fluency and Clock Drawing tests (NEUPSILIN) for executive functions, and the Hospital Anxiety and Depression Scale (HADS). RESULTS: The BNIS score was significantly below reference values in all subscales, especially affect and memory. Verbal Fluency and Clock Drawing subtest results were also lower. Patients with PASC tested high for anxiety/depression, but there was no statistically significant relationship between HADS and BNIS scores. Neuropsychological evaluations showed no differences in cognitive or psychiatric profiles between hospitalized and non-hospitalized patients. CONCLUSIONS: Neuropsychological results suggest executive function problems and high incidence of anxiety/depression, irrespective of acute-phase severity, underscoring a need for neurorehabilitation programs while providing data for public policy initiatives.

Omega-3 Supplementation Prevents Short-Term High-Fat Diet Effects on the α7 Nicotinic Cholinergic Receptor Expression and Inflammatory Response.

The study is aimed at investigating if PUFA supplementation could prevent the effects of a short-term HFD on α7nAChR expression and on the severity of sepsis. Swiss mice were used for the in vivo experiments. For the in vitro experiments, we used a microglia cell line (BV-2) and a hepatoma cell line (Hepa-1c1c7) derived from mice. The animals were either fed standard chow, fed a short-term HFD (60%), or given supplementation with omega-3 fatty acid (2 g/kg or 4 g/kg bw) for 17 days, followed by a short-term HFD. Endotoxemia was induced with an intraperitoneal (i.p.) lipopolysaccharide injection (LPS, 5 or 12 mg/kg), and sepsis was induced by subjecting the animals to cecal ligation and puncture (CLP). BV-2 and Hepa-1c1c7 cells were treated with LPS (100 and 500 ng/mL, respectively) for 3 hours. RT-PCR or Western blotting was used to evaluate α7nAChR expression, inflammatory markers, DNMT1, and overall ubiquitination. LPS and HFD reduced the expression of α7nAChR and increased the expression of inflammatory markers. Omega-3 partially prevented the damage caused by the HFD to the expression of α7nAChR in the bone marrow and hypothalamus, decreased the inflammatory markers, and reduced susceptibility to sepsis-induced death. Exposing the BV-2 cells to LPS increased the protein content of DNMT1 and the overall ubiquitination and reduced the expression of α7nAChR. The inflammation induced by LPS in the BV-2 cell decreased α7nAChR expression and concomitantly increased DNMT1 expression and the ubiquitinated protein levels, indicating the participation of pre- and posttranscriptional mechanisms.

The efficacy of 8-hydroxyquinoline derivatives in controlling the fungus Ilyonectria liriodendri, the causative agent of black foot disease in grapevines.

AIM: The purpose of this study was to evaluate the in vitro and in vivo efficiency of derivatives of 8-Hydroxyquinoline (8HQ) in controlling the fungus Ilyonectria liriodendri. METHODS AND RESULTS: The in vitro tests consisted of assessing its susceptibility to the minimal inhibitory concentration (MIC) and the inhibition of mycelial growth. While the in vivo tests consisted of applying and assessing the most effective products for the protection of wounds, in both preventive + curative and curative forms. The MIC values for PH 151 (6·25 µg ml-1 ) showed better results when compared to the fungicides tebuconazole (>50 µg ml-1 ) and mancozeb (12·5 µg ml-1 for strain 176 and 25 µg ml-1 for strain 1117). PH 151 significantly inhibited mycelial growth, while mancozeb did not differ from the control. In in vivo tests, PH 151 again demonstrated excellent results in vitro, especially when applied preventively. CONCLUSIONS: The derivative of 8HQ PH 151 was effective in controlling the fungus I. liriodendri in vitro and proved to be a promising option for protecting wounds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study points to the prospect of an effective and safe preventive antifungal product, which would enable the use of pesticides in vine culture to be reduced.

Relationship Between Stink Bug Populations in Winter Shelters and Atmospheric Variables in Soybean Growing Areas in Southern Brazil.

Stink bugs (Pentatomidae) are among the main entomological problems in the international farming. Their ability in using alternative plants (refuges) during the off-season is one of the reasons that led them to the status of key pests in several crops. Like other insect species, stink bugs are subject to atmospheric variations. Therefore, the objective of this experiment was to evaluate the abundance, the co-occurrence, and its variations according to the weather in the off-season. The work was conducted between 2014 and 2018, in the municipality of Cruz Alta, state of Rio Grande do Sul (RS), Brazil. Every year, refuges formed by Poaceae and located around the cropped area were evaluated in the second fortnight of June, corresponding to the beginning of the winter solstice. Atmospheric variables corresponding to the evaluation period were used to explain the variation in the populations. In short, our results demonstrated interannual variations in the population abundance of stink bugs in the evaluated refuges. We also found variations in the co-occurrence between species. Finally, we demonstrate the trend in the increase in these refuges in years with cold and dry off-seasons.

Lipid excess affects chaperone-mediated autophagy in hypothalamus.

Obesity is a major health problem worldwide. Overweight and obesity directly affect health-related quality of life and also have an important economic impact on healthcare systems. In experimental models, obesity leads to hypothalamic inflammation and loss of metabolic homeostasis. It is known that macroautophagy is decreased in the hypothalamus of obese mice but the role of chaperone-mediated autophagy is still unknown. In this study, we aimed to investigate the role of hypothalamic chaperone-mediated autophagy in response to high-fat diet and also the direct effect of palmitate on hypothalamic neurons. Mice received chow or high-fat diet for 3 days or 1 week. At the end of the experimental protocol, chaperone-mediated autophagy in hypothalamus was investigated, as well as cytokines expression. In other set of experiments, neuronal cell lines were treated with palmitic acid, a saturated fatty acid. We show that chaperone-mediated autophagy is differently regulated in response to high-fat diet intake for 3 days or 1 week. Also, when hypothalamic neurons are directly exposed to palmitate there is activation of chaperone-mediated autophagy. High-fat diet causes hypothalamic inflammation concomitantly to changes in the content of chaperone-mediated autophagy machinery. It remains to be studied the direct role of inflammation and lipids itself on the activation of chaperone-mediated autophagy in the hypothalamus in vivo and also the neuronal implications of chaperone-mediated autophagy inhibition in response to obesity.

Secondary origin, hybridization and sexual reproduction in a diploid-tetraploid contact zone of the facultatively apomictic orchid Zygopetalum mackayi.

The production of triploids and apomictic reproduction are important processes for polyploid establishment and cytotype coexistence, but we know little about the interaction between triploids and facultatively apomictic plants. To bridge this gap, we studied the pollen-dependent, facultatively apomictic orchid Zygopetalum mackayi from high-elevation outcrops of southeast Brazil. We described the nature of the contact between Z. mackayi cytotypes and patterns of genetic diversity and structure based on eight microsatellite markers and 155 individuals of pure tetraploid, pure diploid and mixed cytotype populations. Our results revealed high values of genetic and genotypic diversity within all populations of Z. mackayi. Each cytotype emerged as a genetic distinct cluster, combining individuals from different populations. Triploids clustered in an intermediate position between diploids and tetraploids. Most genetic variance is associated with individuals within populations and genetic differentiation is high among populations. Mixed cytotype populations of Z. mackayi originate from secondary contact. Triploids are hybrids between diploids and tetraploids and likely act as a bridge. Our results point to the predominance of sexual reproduction in all populations but do not corroborate previous basic chromosome number for this species. Polyploidy rather than facultative apomixis may explain the larger geographic distribution of tetraploids of Z. mackayi.

Changes in cardiac biomarkers in goats naturally affected by pregnancy toxemia.

Pregnancy toxemia (PT) is considered one of the most common metabolic diseases with high impact on the production of small ruminants. The objective of this study was investigate possible myocardial damage in goats affected with PT by the determination of serum myocardial biomarkers CK-MB and cTnI. A total of 44 goats affected with PT, and 10 apparently healthy goats (control group or CG) were used in the study. In goats with PT, the serum concentrations of cTnI (0.43 ng/mL) were significantly higher than that in CG goats (0.06 ng/mL). Although CK-MB showed no significant difference, it was approximately three times higher in animals with PT. The serum concentrations of insulin were significantly lower in PT goats (5.03 ppmol/L) compared to CG goats (10.66 pmol/L). The serum concentrations of cortisol in PT goats (155.41 nmol/L) were significantly higher than that in CG goats (36.58 nmol/L). Results of this study indicate that a clinically significant myocardial damage might occur in goats affected with PT leading to significant elevations in values of cTnI and CK-MB. Therefore, these parameters could be used as a potential prognostic indicator in goats affected with this important disease.

Maternal high fat diet consumption reduces liver alpha7 nicotinic cholinergic receptor expression and impairs insulin signalling in the offspring.

The activation of nicotinic acetylcholine receptor α7 subunit (α7nAChR) has been associated to anti-inflammatory response in macrophages. High-fat diet (HFD) consumption during pregnancy and lactation impairs the cholinergic anti-inflammatory pathway in liver and white adipose tissue of offspring. In order to evaluate the relationship between damage in the cholinergic anti-inflammatory pathway and insulin resistance (IR) development, the liver of offspring of obese dams was investigated. Additionally, the capacity of α7nAChR activation to reduce IR induced by saturated fatty acid was investigated in hepatoma cell line. Initially, female mice were subjected to either standard chow (SC) or HFD during pregnancy and lactation period. After weaning, only male offspring from HFD dams (HFD-O) and SC dams (SC-O) were fed with the SC diet. Hepatic α7nAChR expression was downregulated, and hepatic TNF-α, IL-1ß, and pIKK level, but not pJNK, were elevated in the HFD-O compared to SC-O mice. Besides, hepatic expression of TNF-α in response to lipopolysaccharide (LPS) was higher in HFD-O than SC-O mice. Insulin-stimulated phosphorylation of the AKT was lower in HFD-O compared to SC-O. Additionally, insulin-stimulated phosphorylation of the AKT in KOα7Alb-Cre mice fed HFD was lower than WT mice fed HFD. In hepatoma cell line, palmitate increased IL-6 and TNF-α expressions and pJNK level. These effects were accompanied by reduced capacity of insulin to stimulate AKT phosphorylation. PNU or nicotine reduced cytokine expression and JNK activation, but improved insulin resistance induced by palmitate. Our results suggest that maternal obesity impairs hepatic α7nAChR expression and AKT phosphorylation in the offspring. In vitro studies suggest that α7nAChR activation has potential to reduce deleterious effect of saturated fatty acids on insulin signalling.

Permeation of beta-defensin-3 encapsulated with polyethylene glycol in lung surfactant models at air-water interface.

Coarse grained molecular dynamics of the permeation of the peptide human beta-defensin-3 (HBD3) in two different lung surfactant models (BLES and CUROSURF) at surface tension of 20 mN m-1 was performed in order to simulate the effect of charge distribution on the permeation process. We found that HBD3 permeates in lung surfactant models at surface tension of 20 mN m-1. However, it sticks to the phospholipid polar heads, possibly having its bactericidal properties inactivated by electrostatic interaction. The HBD3 encapsulated with polyethylene glycol (PEG) molecules does permeate, but it does not interact with the polar heads. The Gibbs free energies of this process in both models were estimated to be -39 and -64 Kcal mol-1 for HBD3 and PEG-encapsulated HBD3, respectively. The peptide HBD3 was pulled from the polar heads to the water phase overcoming an energy barrier of around 17 and 22 Kcal mol-1, respectively. The peptide was encapsulated with PEG molecules in order to reduce this barrier, thereby decreasing to roughly 12 and 0 Kcal mol-1 in BLES and CUROSURF models, respectively. After permeation of the HBD3 encapsulated with PEG, it freely moves in the water phase with little or none interaction with the phospholipid head groups. Lung surfactant with low charge distribution seems to have less or none electrostatic interaction with HBD3, possibly preserving its antimicrobial activity.

Effects of auriculotherapy and midazolam for anxiety control in patients submitted to third molar extraction.

Anxiety is common and still represents a barrier to appropriate professional care for patients requiring dental treatment. The aim of this study was to compare the effects of auriculotherapy and midazolam for the control of anxiety in patients submitted to third molar extractions. This was a randomized, double-blind, controlled, crossover clinical trial. Thirty healthy volunteers requiring bilateral third molar extraction received midazolam 15mg (oral) and sham auriculotherapy during one session, and a placebo tablet (oral) and auriculotherapy during the other; the sessions were randomized. The level of anxiety was assessed through questionnaires and physical parameters (blood pressure, heart rate, and oxygen saturation (SpO2)) at three time points: baseline, on the day of surgery, and at follow-up. No significant differences between the protocols were observed for blood pressure and SpO2. Auriculotherapy induced a lower heart rate than midazolam during some periods. Auriculotherapy induced more events remembered after surgery than midazolam (P<0.0001). More undesirable effects were observed with midazolam (P<0.0001). However, patient preference for auriculotherapy (53.3%) was not higher than preference for midazolam (46.7%). Auriculotherapy showed an anxiolytic effect equivalent to the midazolam effect, without the undesirable effects usually attributed to the benzodiazepine.

Percepção de enfermeiros da Estratégia de Saúde da Família sobresegurança do paciente / Family Health Strategy nurses' perception of patient safety

Objetivo: conhecer a percepção de enfermeiros da Estratégia de Saúde da Família sobre segurança do paciente. Métodos: pesquisa qualitativa, realizada em 2016 com 10 enfermeiros, no sul do Brasil,por meio de entrevistas submetidas à Análise de Conteúdo. Resultados: salienta-se a falta de familiarização dos enfermeiros com o assunto. Erros de medicação e quedas foram problemas à segurança dos pacientes e a comunicação efetiva fator promotor. A capacitação das equipes,implementação de instrumentos próprios voltados à segurança do paciente e diminuição da sobrecarga de trabalho foram apontadas enquanto estratégias de melhoria para a segurança do paciente.Considerações finais: o tema segurança do paciente ainda não faz parte da assistência dos enfermeiros da Saúde da Família, mas esses percebem sua importância. Uma cultura de segurança precisa ser implementada nos serviços mediante capacitação desses profissionais por meio de parceria com instituições de ensino.

Objective: to understand the Family Health Strategy nurses’ perception of patient safety. Methods:qualitative research was conducted in 2016 with 10 nurses, in southern Brazil, through interviewssubmitted to Content Analysis. Results: the nurses’ lack of familiarity with the subject ishighlighted. Medication errors and falls were problems to patient safety and effectivecommunication is a promoting factor. The training of teams, implementation of own instrumentsfocused at patient safety and reduction of work overload were pointed out as improvement strategies for patient safety. Final Considerations: the theme of patient safety is not yet part of the assistanceof Family Health nurses, but they realize the importance of this. A safety culture needs to beimplemented in services by training nurses through partnership with educational institutions.

Penetration of antimicrobial peptides in a lung surfactant model.

Molecular dynamics simulations were successfully performed to understand the absorption mechanism of antimicrobial peptides LL-37, CATH-2, and SMAP-29 in a lung surfactant model. The antimicrobial peptides quickly penetrate in the lung surfactant model in dozens or hundreds nanoseconds, but they electrostatically interact with the lipid polar heads during the simulation time of 2 µs. This electrostatic interaction should be the explanation for the inactivation of the antimicrobial peptides when co-administrated with lung surfactant. As they strongly interact with the lipid polar heads of the lung surfactant, there is no positive charge available on the antimicrobial peptide to attack the negatively charged bacteria membrane. In order to avoid the interaction of peptides with the lipid polar heads, sodium cholate was used to form nanoparticles which act as an absorption enhancer of all antimicrobial peptides used in this investigation. The nanoparticles of 150 molecules of sodium cholate with one peptide were inserted on the top of the lung surfactant model. The nanoparticles penetrated into the lung surfactant model, spreading the sodium cholate molecules around the lipid polar heads. The sodium cholate molecules seem to protect the peptides from the interaction with the lipid polar heads, leaving them free to be delivered to the water phase. The penetration of peptides alone or even the peptide nanoparticles with sodium cholate do not collapse the lung surfactant model, indicating to be a promisor drug delivery system to the lung. The implications of this finding are that antimicrobial peptides may only be co-administered with an absorption enhancer such as sodium cholate into lung surfactant in order to avoid inactivation of their antimicrobial activity.

Effects of passiflora incarnata and midazolam for control of anxiety in patients undergoing dental extraction.

BACKGROUND: Anxiety symptoms are frequently observed in dental patients, whether they are undergoing simple or more invasive procedures such as surgery. This research aimed to compare the effects of Passiflora incarnata and midazolam for the control of anxiety in patients undergoing mandibular third molar extraction. MATERIAL AND METHODS: Forty volunteers underwent bilateral extraction of their mandibular third molars in a randomized, controlled, double-blind, crossover clinical trial. Passiflora incarnata (260 mg) or midazolam (15 mg) were orally administered 30 minutes before surgery. The anxiety level of participants was evaluated by questionnaires and measurement of physical parameters, including heart rate (HR), blood pressure (BP), and oxygen saturation (SpO2). RESULTS: Considering each procedure independently, there were no significant differences between the protocols in BP, HR, and SpO2. Over 70% of the volunteers responded that they felt quiet or a little anxious under both protocols. With midazolam, 20% of the participants reported amnesia (not remembering anything at all), while Passiflora showed little or no ability to interfere with memory formation. CONCLUSIONS: Passiflora incarnata showed an anxiolytic effect similar to midazolam, and was safe and effective for conscious sedation in adult patients who underwent extraction of their mandibular third molars.

Hypothalamic stearoyl-CoA desaturase-2 (SCD2) controls whole-body energy expenditure.

BACKGROUND/OBJECTIVES: Stearoyl-CoA desaturase-2 (SCD2) is the main δ9 desaturase expressed in the central nervous system. Because of its potential involvement in controlling whole-body adiposity, we evaluated the expression and function of SCD2 in the hypothalami of mice. SUBJECTS/METHODS: Male mice of different strains were used in real-time PCR, immunoblot and metabolic experiments. In addition, antisense oligonucleotides and lentiviral vectors were used to reduce and increase the expression of SCD2 in the hypothalamus. RESULTS: The level of SCD2 in the hypothalamus is similar to other regions of the central nervous system and is ~10-fold higher than in any other region of the body. In the arcuate nucleus, SCD2 is expressed in proopiomelanocortin and neuropeptide-Y neurons. Upon high fat feeding, the level of hypothalamic SCD2 increases. Inhibition of hypothalamic SCD2 as accomplished by two distinct approaches, an antisense oligonucleotide or a short-hairpin RNA delivered by a lentivirus, resulted in reduced body mass gain mostly due to increased energy expenditure and increased spontaneous activity. Increasing hypothalamic SCD2 by a lentivirus approach resulted in no change in body mass and food intake. CONCLUSIONS: Thus, SCD2 is highly expressed in the hypothalami of rodents and its knockdown reduces body mass due to increased whole-body energy expenditure.

Coccinellidae Parasitoids in Brazil: Neglected Species in a Mega-Diverse Country.

Current knowledge on coccinellids is primarily focused on their role as natural enemies of soft-bodied insects. However, there is a great diversity of coccinellid parasitoid species that are less studied. Here, we describe new records of coccinellid parasitoids with emphasis on new host-parasitoid interactions in 11 sample sites in Brazil. We collected 122 coccinellid individuals parasitized by six species of parasitoids in the Cerrado and in the Atlantic Rainforest biomes. New records of coccinellid parasitoids and host associations, expansion of habitat ranges and interactions are discussed focusing on the lack of basic information on these interactions in Brazil.

Body size evolution in Titanosauriformes (Sauropoda, Macronaria).

Titanosauriformes is a conspicuous and diverse group of sauropod dinosaurs that inhabited almost all land masses during Cretaceous times. Besides the diversity of forms, the clade comprises one of the largest land animals found so far, Argentinosaurus, as well as some of the smallest sauropods known to date, Europasaurus and Magyarosaurus. They are therefore good candidates for studies on body size trends such as the Cope's rule, the tendency towards an increase in body size in an evolutionary lineage. We used statistical methods to assess body size changes under both phylogenetic and nonphylogenetic approaches to identify body size trends in Titanosauriformes. Femoral lengths were collected (or estimated from humeral length) from 46 titanosauriform species and used as a proxy for body size. Our findings show that there is no increase or decrease in titanosauriform body size with age along the Cretaceous and that negative changes in body size are more common than positive ones (although not statistically significant) for most of the titanosauriform subclades (e.g. Saltasaridae, Lithostrotia, Titanosauria and Somphospondyli). Therefore, Cope's rule is not supported in titanosauriform evolution. Finally, we also found a trend towards a decrease of titanosauriform mean body size coupled with an increase in body size standard deviation, both supporting an increase in body size variation towards the end of Cretaceous.

Maternal high-fat diet consumption modulates hepatic lipid metabolism and microRNA-122 (miR-122) and microRNA-370 (miR-370) expression in offspring.

Maternal consumption of a high-fat diet (HFD) during pregnancy and lactation is closely related to hepatic lipid accumulation, insulin resistance and increased serum cytokine levels in offspring and into their adulthood. MicroRNA (miRNA) have been implicated in cholesterol biosynthesis and fatty acid metabolism. We evaluated the modulation of hepatic fatty acid synthesis (de novo), ß-oxidation pathways, and miRNA-122 (miR-122) and miRNA-370 (miR-370) expression in recently weaned offspring (day 28) of mouse dams fed a HFD (HFD-O) or a standard chow (SC-O) during pregnancy and lactation. Compared with SC-O mice, HFD-O mice weighed more, had a larger adipose tissue mass and were more intolerant to glucose and insulin (P< 0·05). HFD-O mice also presented more levels of serum cholesterol, TAG, NEFA and hepatic IκB kinase and c-Jun N-terminal kinase phosphorylation compared with SC-O mice (P< 0·05). Protein levels of fatty acid synthase, acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase were similar in HFD-O and SC-O mice, whereas expression levels of SCD1 mRNA and protein were more abundant in HFD-O mice than in SC-O mice (P< 0·05). Interestingly, mRNA expression levels of the ß-oxidation-related genes ACADVL and CPT1 were decreased in HFD-O mice (P< 0·05). Furthermore, the expression of miR-122 was reduced but that of miR-370 was increased in HFD-O mice compared with that in SC-O mice (P< 0·05). Changes in hepatic lipid metabolism were accompanied by increased mRNA content of AGPAT1 and TAG deposition in HFD-O mice (P< 0·05). Taken together, the present results strongly suggest that maternal consumption of a HFD affects the early lipid metabolism of offspring by modulating the expression of hepatic ß-oxidation-related genes and miRNA that can contribute to metabolic disturbances in adult life.

Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae).

The anti-nociceptive and antioxidant activities of the Anadenantheracolubrina stem bark aqueous extract (AEAC) were investigated. AEAC (30 µg/mL) reduced 94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 µg/mL) of lipid peroxidation caused by 2,2'-azobis(2-methylpropionamidine) dihydrochloride-induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly (p < 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test. Nociception caused by glutamate was significantly (p < 0.001) reduced by up to 79% at 400 mg/kg, while 56-60% of the nociceptive behaviour induced by capsaicin was significantly inhibited by AEAC (100-400 mg/kg). Mice treated with AEAC did not show changes in motor performance in the Rota-rod apparatus. It appears that AEAC is of pharmacological importance in treating pain due to its anti-nociceptive effects, which were shown to be mediated by central and peripheral mechanisms.