Evaluation of the Effects of Extracts Containing Valeriana officinalis and Piper methysticum on the Activities of Cytochrome P450 3A and P-Glycoprotein.

This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.

Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST). METHODS: Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs. RESULTS: The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo. CONCLUSIONS: Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models.

Simulating adaptive grazing management on soil organic carbon in the Southeast U.S.A. using MEMS 2.

Grazing lands play a significant role in global carbon (C) dynamics, holding substantial soil organic carbon (SOC) stocks. However, historical mismanagement (e.g., overgrazing and land-use change) has led to substantial SOC losses. Regenerative practices, such as adaptive multi-paddock (AMP) grazing, offer a promising avenue to improve soil health and help combat climate change by increasing SOC accrual, both in its particulate (POC) and mineral-associated (MAOC) organic C components. Because adaptive grazing patterns emerge from the combination of different levers such as frequency, intensity, and timing of grazing, studying AMP grazing management in experimental trials and representing it in models remains challenging. Existing ecosystem models lack the capacity to predict how different adaptive grazing levers affect SOC storage and its distribution between POC and MAOC and along the soil profile accurately. Therefore, they cannot adequately assist decision-makers in effectively optimizing adaptive practices based on SOC outcomes. Here, we address this critical gap by developing version 2.34 of the MEMS 2 model. This version advances the previous by incorporating perennial grass growth and grazing submodules to simulate grass green-up and dormancy, reserve organ dynamics, the influence of standing dead plant mass on new plant growth, grass and supplemental feed consumption by animals, and their feces and urine input to soil. Using data from grazing experiments in the southeastern United States and experimental SOC data from two conventional and three AMP grazing sites in Mississippi, we tested the capacity of MEMS 2.34 to simulate grass forage production, total SOC, POC, and MAOC dynamics to 1-m depth. Further, we manipulated grazing management levers, i.e., timing, intensity, and frequency, to do a sensitivity analysis of their effects on SOC dynamics in the long term. Our findings indicate that the model can represent bahiagrass forage production (BIAS = 9.51 g C m-2, RRMSE = 0.27, RMSE = 65.57 g C m-2, R2 = 0.72) and accurately captured the dynamics of SOC fractions across sites and depths (0-15 cm: RRMSE = 0.05; 15-100 cm: RRMSE = 1.08-2.07), aligning with patterns observed in the measured data. The model best captured SOC and MAOC stocks across AMP sites in the 0-15 cm layer, while POC was best predicted at-depth. Otherwise, the model tended to overestimate SOC and MAOC below 15 cm, and POC in the topsoil. Our simulations indicate that grazing frequency and intensity were key levers for enhancing SOC stocks compared to the current management baseline, with decreasing grazing intensity yielding the highest SOC after 50 years (63.7-65.9 Mg C ha-1). By enhancing our understanding of the effects of adaptive grazing management on SOC pools in the southeastern U.S., MEMS 2.34 offers a valuable tool for researchers, producers, and policymakers to make AMP grazing management decisions based on potential SOC outcomes.

Exercise improves respiratory function, body fluid and nitric oxide in hemodialysis patients.

Emerging evidence suggests that resistance training (RT) can mitigate respiratory muscle weakness in hemodialysis (HD) patients. However, the underlying mechanisms responsible for these beneficial effects remain unclear. The purpose of this study was to assess the impact of periodized RT on respiratory muscle strength and its relationship with handgrip strength (HGS), fat-free mass (FFM), nitric oxide (NO), and interdialytic weight gain (IWG) in HD patients. Thirty-three patients were randomly assigned to two groups: control (CTL; n=18) and RT (n=15). RT group did not perform any additional exercise training specific to the respiratory tract. Maximal inspiratory (MIP) and expiratory (MEP) pressures, peak expiratory flow (PEF), HGS, FFM, NO, and IWG were measured before and after the intervention period. Participants in the RT group engaged in a 24-week RT program, three times per week. RT resulted in significant improvements in MIP, MEP, PEF, as well as enhancements in HGS, FFM, NO, and IWG (p<0.05). Notably, inverse correlations were observed between MIP (r= -0.37, p=0.03) and PEF (r= -0.4, p=0.02) with IWG. Thus, the amelioration of HGS and FFM coincided with a reduction in respiratory muscle weakness among HD patients. Decreased IWG and increased circulating NO are plausible mechanisms contributing to these improvements.

Effect of Preoperative Bilateral Ultrasound-guided Quadratus Lumborum Nerve Block on Quality of Recovery after Minimally Invasive Hysterectomy in an Enhanced Recovery after Surgery (ERAS) Setting.

STUDY OBJECTIVE: To assess the effect of preoperative bilateral ultrasound-guided quadratus lumborum nerve block (QLB) on quality of recovery after minimally invasive hysterectomy, in an enhanced recovery after surgery setting. DESIGN: Randomized, controlled, double-blinded trial (Canadian Task Force level I). SETTING: University-affiliated tertiary medical center. PATIENTS: All women undergoing an elective robotic or laparoscopic hysterectomy. Women with chronic pain, chronic anticoagulation, and body mass index >50 kg/m2 were excluded. INTERVENTION: Patients were randomized with a 1:1 allocation, to one of the following 2 arms, and stratified based on robotic versus laparoscopic approach. 1. QLB: QLB (bupivacaine) + sham local trocar sites infiltration (normal saline) 2. Local infiltration: sham QLB (normal saline) + local infiltration (bupivacaine) MEASUREMENTS AND MAIN RESULTS: The primary outcome was defined as the quality of recovery score based on the validated questionnaire Quality of Recovery, completed 24 hours postoperatively. Secondary outcomes included dynamic pain scores, accumulated opioid consumption up to 24 hours, postoperative nausea and vomiting, surgical complications, length of hospital stay, time to first pain medication administration in the postanesthesia care unit, and adverse events. A total of 76 women were included in the study. Demographic characteristics were similar in both groups. Median age was 44 years (interquartile range 39-50), 47% of the participants were African American, and mean body mass index was 32.8 kg/m2 (standard deviation [SD] 8.1). The mean Quality of Recovery score was 179.1 (SD ± 10.3) in the QLB and 175.6 (SD ± 9.7) for the local anesthesia group (p = .072). All secondary outcomes were comparable between groups. CONCLUSIONS: QLBs do not significantly improve quality of recovery after elective robotic or laparoscopic hysterectomy compared with local anesthetic port site infiltration.

Should a Stoma Be Used After Intestinal Transplant.

As we all acknowledge benefits of ostomies, they can come with significant morbidity, quality of life issues, and major complications, especially during reversal procedures. In recent years, we have started to observe that similar graft and patient survival can be achieved without ostomies in certain cases. This observation and practice adopted in a few large-volume transplant centers opened a new discussion about the necessity of ostomies in intestinal transplantation. There is still more time and randomized studies will be needed to better understand and analyze the risk/benefits of "No-ostomy" approach in intestinal transplantation.

Effects of a Single Dose of Ayahuasca in College Students With Harmful Alcohol Use: A Single-blind, Feasibility, Proof-of-Concept Trial.

BACKGROUND: Ayahuasca is a South American plant hallucinogen rich in the psychedelic N,N-dimethyltryptamine and ß-carbolines (mainly harmine). Preclinical and observational studies suggest that ayahuasca exerts beneficial effects in substance use disorders, but these potentials were never assessed in a clinical trial. METHODS: Single-center, single-blind, feasibility, proof-of-concept study, assessing the effects of one dose of ayahuasca accompanied by psychological support (without psychotherapy) on the drinking patterns (primary variable) of 11 college students with harmful alcohol consumption. Secondary variables included safety and tolerability, craving, personality, anxiety, impulsivity, self-esteem, and social cognition. FINDINGS: Ayahuasca was well tolerated (no serious adverse reactions were observed), while producing significant psychoactive effects. Significant reductions in days per week of alcohol consumption were found between weeks 2 and 3 (2.90 ± 0.28 vs 2.09 ± 0.41; P < 0.05, uncorrected), which were not statistically significant after Bonferroni correction. There were no statistically significant effects for other variables, except for a significant reduction in reaction time in an empathy task. CONCLUSIONS: A significant reduction in days of alcohol consumption was observed 2-3 weeks after ayahuasca intake, but this effect did not survive after Bonferroni correction. The lack of significant effects in alcohol use and other variables may be related to the small sample size and mild/moderate alcohol use at baseline. The present study shows the feasibility of our protocol, paving the way for future larger, controlled studies.

Nonlinear hydrological time series modeling to forecast river level dynamics in the Rio Negro Uruguay basin.

Floods significantly impact the well-being and development of communities. Hence, understanding their causes and establishing methodologies for risk prevention is a critical challenge for effective warning systems. Complex systems such as hydrological basins are modeled through hydrological models that have been utilized to understand water recharge of aquifers, available volume of dams, and floods in diverse regions. Acquiring real-time hydrometeorological data from basins and rivers is vital for establishing data-driven-based models as tools for the prediction of river-level dynamics and for understanding its nonlinear behavior. This paper introduces a hydrological model based on a multilayer perceptron neural network as a useful tool for time series modeling and forecasting river levels in three stations of the Rio Negro basin in Uruguay. Daily time series of river levels and rainfall serve as the input data for the model. The assessment of the models is based on metrics such as the Nash-Sutcliffe coefficient, the root mean square error, percent bias, and volumetric efficiency. The outputs exhibit varying model performance and accuracy during the prediction period across different sub-basin scales, revealing the neural network's ability to learn river dynamics. Lagged time series analysis demonstrates the potential for chaos in river-level time series over extended time periods, mainly when predicting dam-related scenarios, which shows physical connections between the dynamical system and the data-based model such as the evolution of the system over time.

Long-term ayahuasca use is associated with preserved global cognitive function and improved memory: a cross-sectional study with ritual users.

Although several studies have been conducted to elucidate the relationship between psychedelic consumption and cognition, few have focused on understanding the long-term use influence of these substances on these variables, especially in ritualistic contexts.  To verify the influence of ritualistic ayahuasca consumption on the cognition of experienced ayahuasca religious users (> 20 years) and beginners (< 3 years), which participated in rituals of the Centro Luz Divina (CLD), a Santo Daime church in Brazil. Observational, descriptive, and cross-sectional study was carried out in which 48 people participated divided into three groups: (a) experienced ayahuasca users (n = 16), (b) beginner ayahuasca users (n = 16) and (c) control group (n = 16). All groups were matched by sex, age, and education and contained 8 women and 8 men. Cognition was assessed with the WASI (intelligence quotient), Digit Span (verbal working memory), Corsi Block-Tapping Task (visuospatial-related and working memory), Rey-Osterrieth Complex Figure test (visual perception, immediate memory), and Wisconsin Card Sorting and Five Digit Test (executive functions). Groups were homogenous in terms of sociodemographic characteristics, with participants presenting average intellectual performance. There was no evidence of cognitive decline amongst ayahuasca users. The experienced group showed higher scores compared to the less experienced group in the Digit Span and Corsi Block-Tapping tasks, which assess working verbal and visuospatial memories respectively. We confirmed the botanical identities of Psychotria viridis and Banisteriopsis caapi and the presence of the alkaloids both in the plants and in the brew. Short and long-term ayahuasca consumption does not seem to alter human cognition, while long-term use seems to be associated with improvements in aspects of working memory when compared with short-term use.

A novel approach for the facile synthesis of zinc oxide/carbon hybrid systems from corn distillers soluble: Surface modification and characterization for sustainable remediation.

Sustainable, efficient, and environmentally friendly ways to tailor the carbonaceous materials from bio sources with desired functionalities remain a challenge around the world. In this study, we represent a novel approach to synthesize carbon hybrid material based on Zinc Oxide/carbon (ZnO/C) hybrid systems by catalytic hydrothermal process via crosslinking reaction through nucleation and growth of ZnO particles at the functional groups of oxidized carbon material. This research explored the volarization of Condensed Corn Distillers Soluble (CDS) as a carbon precursor to synthesize biobased carbon spheres. Surface modification of the produced carbon spheres took place using zinc chloride (ZnCl2) during hydrothermal carbonization (HTC). Zinc chloride (ZnCl2) was used to function as a catalyst during HTC and functioned as a ZnO source to synthesize (ZnO/C) hybrid systems. Design Expert software v13 was used to design the hydrothermal carbonization (HTC) experiments and response surface methodology was used to find the optimized conditions for the preparation of carbon hybrid systems. The hydrothermal synthesis process introduced 3D stone like zinc oxide particles onto the carbon matrix. These particles were self-assembled onto the carbon framework to produce carbon hybrid systems with unique physical, chemical, structural and functional properties. Herein, the obtained carbon hybrid systems (ZnO/C) were investigated and discussed in detail. ZnO/C hybrid systems were analyzed for surface morphology using scanning electron microscopy (SEM) that presented a 3D spherical interconnected phase and XRD analyses were used for phase crystallinity that showed new crystalline phases such as hopeite and zincite after the ZnCl2 incorporation. Surface functional groups were also analyzed by FTIR and results confirmed the presence of hydrophilic groups such as -OH, CC, and COOH on the surface of ZnO/C hybrid carbon systems. This study provided the insightful guidance for tailoring novel design of multifunctional carbon material as an adsorbent/catalyst for various applications of sustainable remediation.

Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) per se is a risk factor for thrombosis. Considering the growing body of evidence on blood-flow restriction (BFR) exercise in HD patients, identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model. The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise (RE) with BFR on this molecule. METHODS: Two hundred and six HD patients volunteered for this study (all with a glomerular filtration rate of <15 mL/min/1.73 m2). The RE + BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD (intradialytic exercise). RE repetitions included concentric and eccentric lifting phases (each lasting 2 s) and were supervised by a strength and conditioning specialist. RESULTS: Several variables were associated with elevated levels of D-dimer, including higher blood glucose, citrate use, recent cardiovascular events, recent intercurrents, higher inflammatory status, catheter as vascular access, older patients (>70 years old), and HD vintage. Furthermore, RE + BFR significantly increases D-dimer after 4 h. Patients with borderline baseline D-dimer levels (400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range (≥500 ng/mL). CONCLUSION: These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE + BFR. D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE + BFR.

Endothelial-specific telomerase inactivation causes telomere-independent cell senescence and multi-organ dysfunction characteristic of aging.

It has remained unclear how aging of endothelial cells (EC) contributes to pathophysiology of individual organs. Cell senescence results in part from inactivation of telomerase (TERT). Here, we analyzed mice with Tert knockout specifically in EC. Tert loss in EC induced transcriptional changes indicative of senescence and tissue hypoxia in EC and in other cells. We demonstrate that EC-Tert-KO mice have leaky blood vessels. The blood-brain barrier of EC-Tert-KO mice is compromised, and their cognitive function is impaired. EC-Tert-KO mice display reduced muscle endurance and decreased expression of enzymes responsible for oxidative metabolism. Our data indicate that Tert-KO EC have reduced mitochondrial content and function, which results in increased dependence on glycolysis. Consistent with this, EC-Tert-KO mice have metabolism changes indicative of increased glucose utilization. In EC-Tert-KO mice, expedited telomere attrition is observed for EC of adipose tissue (AT), while brain and skeletal muscle EC have normal telomere length but still display features of senescence. Our data indicate that the loss of Tert causes EC senescence in part through a telomere length-independent mechanism undermining mitochondrial function. We conclude that EC-Tert-KO mice is a model of expedited vascular senescence recapitulating the hallmarks aging, which can be useful for developing revitalization therapies.

Solvent-free parallel artificial liquid membrane extraction for drugs of abuse in plasma samples using LC-MS/MS.

BACKGROUND: Parallel artificial liquid membrane extraction (PALME) is a 96-well plate setup variant of liquid-phase microextraction. Basic or acidic analytes are extracted in neutral form from the sample, through a supported liquid membrane (SLM), and into aqueous acceptor. PALME is already considered a green extraction technique, but in the current conceptual work, we sought to make it even greener by replacing the use of organic solvents with essential oils (EO). PALME was combined with LC-MS/MS for analysis of plasma samples and multiple drugs of abuse with toxicological relevance (amphetamines, phenethylamines, synthetic cathinones, designer benzodiazepines, ayahuasca alkaloids, lysergic acid diethylamide, and ketamine). RESULTS: Fourteen EO were compared to organic solvents frequently used in PALME. The EO termed smart & sassy yielded the best analyte recovery for all drugs studied and was thus selected as SLM. Then, factorial screening and Box-Behnken were employed to optimize the technique. The extraction time, concentration of base, sample volume, and percentage of trioctylamine significantly impacted analyte recovery. The optimum values were defined as 120 min, 10 mmol/L of NaOH, 150 µL, and 0%, respectively. Once optimized, validation parameters were 1-100 ng mL-1 as linear range, accuracy ±16.4%, precision >83%, 1 ng mL-1 as limit of quantitation, 0.1-0.75 ng mL-1 as limit of detection, matrix effect <20%, and recovery 20-106%. Additionally, EO purchased from different production batches were tested and achieved acceptable reproducibility. Data were in compliance with requirements set by internationally accepted validation guidelines and the applicability of the technique was proven using authentic samples. SIGNIFICANCE: In this study, the use of an EO provided a solvent-free sample preparation technique suited to extract different classes of drugs of abuse from plasma samples, dismissing the use of hazardous organic solvents. The method also provided excellent sample clean-up, thus being a simple and efficient tool for toxicological applications that is in agreement with the principles of sustainable chemistry.

Individual transmembrane domains of SfABCC2 from Spodoptera frugiperda do not serve as functional Cry1F receptors.

The fall armyworm (Spodoptera frugiperda) is a major global pest causing severe damage to various crops, especially corn. Transgenic corn producing the Cry1F pesticidal protein from the bacterium Bacillus thuringiensis (Cry1F corn) showed effectiveness in controlling this pest until S. frugiperda populations at locations in North and South America evolved practical resistance. The mechanism for practical resistance involved disruptive mutations in an ATP binding cassette transporter subfamily C2 gene (SfABCC2), which serves as a functional Cry1F receptor in the midgut cells of susceptible S. frugiperda. The SfABCC2 protein contains two transmembrane domains (TMD1 and TMD2), each with a cytosolic nucleotide (ATP) binding domain (NBD1 and NBD2, respectively). Previous reports have demonstrated that disruptive mutations in TMD2 were linked with resistance to Cry1F, yet whether the complete SfABCC2 structure is needed for receptor functionality or if a single TMD-NBD protein can serve as functional Cry1F receptor remains unknown. In the present study, we separately expressed TMD1 and TMD2 with their corresponding NBDs in cultured insect cells and tested their Cry1F receptor functionality. Our results show that the complete SfABCC2 structure is required for Cry1F receptor functionality. Moreover, binding competition assays revealed that Cry1F specifically bound to SfABCC2, whereas neither SfTMD1-NBD1 nor SfTMD2-NBD2 exhibited any significant binding. These results provide insights into the molecular mechanism of Cry1F recognition by SfABCC2 in S. frugiperda, which could facilitate the development of more effective insecticidal proteins.

A covid-19 e a reorganização do processo de trabalho do enfermeiro na atenção primária à saúde / Covid-19 and the reorganization of the nurse's work process in primary health care / Covid-19 y la reorganización del proceso de trabajo de la enfermería en la atención primaria de salud

Objetivo: descrever a experiência da reorganização do processo de trabalho de enfermeiros que atuam na Atenção Primária à Saúde no enfrentamento da covid-19, no município de João Pessoa - Paraíba. Métodos: Trata-se de um estudo descritivo com abordagem qualitativa, desenvolvido com um total de 15 enfermeiras atuantes no município de João Pessoa com idade entre 41 e 67 anos (média de 56 anos) e com tempo médio de 12 anos e 8 meses de atuação na Estratégia Saúde da Família. Resultados: foram evidenciados um campo amplo de alterações na dinâmica das Unidades Básicas de Saúde devido a pandemia, dentre elas, modificações no processo de trabalho da equipe, a estagnação das atividades coletivas, como também a implementação de ações destinadas para a covid-19. Conclusão: As experiências relatadas das participantes do estudo ressaltam o grande impacto que a pandemia trouxe para o cotidiano de uma equipe de Atenção Básica, sendo fundamental o fortalecimento da atenção primária à saúde, com recursos financeiros, incentivo e qualificação profissional, garantindo uma maior adequação da nova realidade vivida, a fim de garantir continuidade do cuidado. (AU)

Objective: to describe the experience of the reorganization of the work process of nurses who work in Primary Health Care in the face of covid-19, in the city of João Pessoa - Paraíba. Methods: This is a descriptive study with a qualitative approach, developed with a total of 15 nurses working in the city of João Pessoa aged between 41 and 67 years (average of 56 years) and with an average time of 12 years and 8 months of performance in the Family Health Strategy. Results: a wide field of changes in the dynamics of Basic Health Units due to the pandemic were evidenced, among them, changes in the team's work process, the stagnation of collective activities, as well as the implementation of actions aimed at covid-19. Conclusion: The reported experiences of the study participants highlight the great impact that the pandemic has brought to the daily life of a Primary Care team, making it essential to strengthen primary health care, with financial resources, incentives and professional qualification, ensuring greater adequacy. of the new lived reality, in order to guarantee continuity of care. (AU)

Objetivo: describir la experiencia de la reorganización del proceso de trabajo de los enfermeros que actúan en la Atención Primaria de Salud frente a la covid-19, en la ciudad de João Pessoa - Paraíba. Métodos: Se trata de un estudio descriptivo con enfoque cualitativo, desarrollado con un total de 15 enfermeros que actúan en la ciudad de João Pessoa con edades entre 41 y 67 años (promedio de 56 años) y con tiempo promedio de 12 años y 8 meses de vida. desempeño en la Estrategia de Salud de la Familia. Resultados: Se evidenció un amplio campo de cambios en la dinámica de las Unidades Básicas de Salud debido a la pandemia, entre ellos, cambios en el proceso de trabajo del equipo, el estancamiento de las actividades colectivas, así como la implementación de acciones dirigidas a la covid-19. Conclusión: Las experiencias relatadas por los participantes del estudio resaltan el gran impacto que la pandemia trajo para el cotidiano de un equipo de Atención Primaria, siendo imprescindible fortalecer la atención primaria de salud, con recursos económicos, incentivos y calificación profesional, asegurando una mayor adecuación. de la nueva realidad vivida, para garantizar la continuidad de la atención. (AU)

Ayahuasca-enhanced extinction of fear behaviour: Role of infralimbic cortex 5-HT2A and 5-HT1A receptors.

BACKGROUND AND PURPOSE: Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N-dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA-treated rats. EXPERIMENTAL APPROACH: We focused on the 5-HT1A and 5-HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis. KEY RESULTS: A single oral treatment with AYA containing 0.3 mg·kg-1 of DMT increased the within-session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1- and 21-day-old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA- and vehicle-treated animals showed no differences when tested in the elevated plus-maze. The 5-HT2A receptor antagonist MDL-11,939 and the 5-HT1A receptor antagonist WAY-100635 infused into the infralimbic cortex respectively blocked within- and between-session fear extinction effects resulting from repeated oral administration of AYA. CONCLUSION AND IMPLICATIONS: Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress-related disorders.

Exploring the impact of short daily haemodialysis on muscle strength and bone health in end-stage kidney disease patients.

BACKGROUND: Short-daily haemodialysis (SDH) has been strongly recommended over conventional haemodialysis (CHD) for end-stage kidney disease patients, though few studies have directly compared the effects of these two haemodialysis (HD) modalities on clinical variables related to patient's health. METHODS: We conducted a cross-sectional study in individuals undergoing HD, comparing epidemiological, clinical, metabolic, inflammatory, anthropometric, bone health/metabolism, and skeletal muscle function according to dialysis modality. One-hundred seventy-eight patients (20.8% females, 62 ± 2.5 years old), were analysed in this study, 86 (48%) of whom were undergoing CHD versus 92 (51%) who were undergoing SDH. RESULTS: SDH patients had significantly higher serum albumin levels (3.93 vs. 3.66 g/dL, P < 0.0001) and higher Kt/v (2.6 vs. 2.38, P < 0.0001). SDH group presented a significantly lower number of erythropoietin-stimulating agents compared with CHD group (percentage: 53.3 vs. 83.7%, P < 0.0001) and had lower levels of serum phosphate (4.9 vs. 5.3 mg/dL, P = 0.004) and parathyroid hormone (PTH) (398.4 vs. 480.4 pg/mL, P < 0.001) compared with CHD patients. In terms of bone health and metabolism, SDH patients had significantly higher total BMD, femur BMD, lumbar BMD, and femoral neck BMD compared with CHD patients (all P < 0.05). SDH patients also had lower anti-osteogenic and inflammatory biomarkers, including FGF23, sclerostin, TNF, IL-18, IL-17a, and C-reactive peptide (all P < 0.05). CHD modality was demonstrated to be a risk factor for low BMD (odds ratio: 4.02; 95% CI: 1.59-10.2, P = 0.003). In terms of skeletal muscle function, SDH patients had significantly higher 6-minute walking test (444.6 vs. 424.9 m, P = 0.04) and higher fat-free mass (52.3 vs. 51.68 kg, P = 0.02) compared with CHD patients. Higher fat-free mass and handgrip strength were associated with a 34% and 23% lower risk of low BMD, respectively. SDH patients had lower levels of the uremic toxin asymmetric dimethyl-l-arginine (ADMA) (1.8 vs. 2.07 µM, P = 0.002) and fasting blood glucose (132.6 vs. 141.7 mg/dL, P < 0.02) than CHD group. SDH patients also displayed higher levels of haemoglobin when compared with CHD group (11.9 vs. 10.2 g/dL, P < 0.0001). CONCLUSIONS: The present study improves our understanding of the relationship between dialysis modality and clinical variables that may influence HD patient's health. Grip strength and lean mass were positively correlated with bone mineral density in HD patients regardless of dialysis modality. SDH was associated with better bone mineral density, inflammatory profile, and skeletal muscle function when compared with CHD patients. These findings provide more evidence of the clinical benefits of SDH that should be explored in greater detail.

Effectiveness and safety of ultra-low-dose spinal anesthesia versus perineal blocks in hemorroidectomy and anal fistula surgery: a randomized controlled trial

Abstract Background: Ultra-low-dose Spinal Anesthesia (SA) is the practice of employing minimal doses of intrathecal agents so that only the roots that supply a specific area are anesthetized. The aim of this study was to compare the effectiveness and safety of ultra-low-dose spinal anesthesia with that of Perineal Blocks (PB). Methods: A two-arm, parallel, double-blind randomized controlled trial comparing two anesthetic techniques (SA and PB) for hemorrhoidectomy and anal fistula surgery was performed. The primary outcomes were postoperative pain, complementation and/or conversion of anesthesia, and hemodynamic changes. Results: Fifty-nine patients were included in the final analysis. The mean pain values were similar in the first 48 h in both groups (p > 0.05). The individuals allocated to the SA group did not need anesthetic complementation; however, those in the PB group required it considerably (SA group, 0% vs. PB group, 25%; p = 0.005). Hemodynamic changes were more pronounced after PB: during all surgical times, the PB group showed lower MAP values and higher HR values (p < 0.05). Postoperative urinary retention rates were similar between both groups (SA group 0% vs. PB group 3.1%, p = 0.354). Conclusion: SA and PB are similarly effective in pain control during the first 48 h after hemorrhoidec-tomy and anal fistula surgery. Although surgical time was shorter among patients in the PB group, the SA technique may be preferable as it avoids the need for additional anesthesia. Furthermore, the group that received perineal blocks was under sedation with a considerable dose of propofol.

Clientes submetidos a Artroplastia total da Anca: As intervenções do Enfermeiro Especialista de Reabilitação / Clients undergoing total hip arthroplasty: The interventions of the Rehabilitation Nurse Specialist

Introdução: A osteoartrose afeta 10% da população acima dos 60 anos e é a doença articular com maior prevalência no mundo afetando as pessoas na realização dos autocuidados. Os referenciais teóricos sustentam a prática de enfermagem, a Teoria do autocuidado de Orem fornece bases conceptuais na prestação de cuidados, no sentido da (in)dependência nos autocuidados. A Enfermagem de Reabilitação constitui-se como uma área de intervenção reconhecida, capaz de dar resposta às necessidades efetivas da população, bem como às exigências nos cuidados, traduzindo-se esse aporte na procura de ganhos em saúde dos clientes nos diversos contextos da sua prática. Objetivos: Descrever as atividades clínicas para o desenvolvimento de competências na área de enfermagem de Reabilitação e apresentar um estudo de investigação com o tema: Clientes submetidos a Artroplastia total da Anca: As intervenções do Enfermeiro Especialista em Enfermagem de Reabilitação. Metodologia: Para a concretização do estudo foi realizada uma Scoping Review com base nas recomendações do Joanna Briggs Institute. Os artigos, selecionados através de uma lista de verificação PRISMA-ScR, incluem os com data de publicação igual e superior ao ano de 2018, nos idiomas português, inglês e espanhol. Resultados: De 420 artigos, 10 foram incluídos nesta Scoping Review. Todos os resultados valorizaram as intervenções do Enfermeiro Especialista de Reabilitação, com contributos relevantes para o cuidado dos doentes submetidos a ATA. Ficou evidenciado que todos os programas de enfermagem de reabilitação devem ser centrados e personalizados para a pessoa que necessita de ajuda do EEER na reconstrução da sua autonomia, durante as diferentes fases do processo de cuidados. Conclusões: Os artigos selecionados e considerados válidos indicam claramente a importância do Enfermeiro de Reabilitação, enquanto contributo direto para o sucesso de um processo de transição saudável e na capacitação do cliente e família/cuidador durante o processo de cuidados. A sua intervenção favorece os ganhos globais na saúde e na reconstrução da autonomia de cliente submetidos a ATA. O desenvolvimento de estudos que analisem as intervenções do Enfermeiro Especialista em Enfermagem de Reabilitação é indispensável para apurar os contributos destes profissionais nesta área.