Association between Gut Microbiota and Inflammation: Mediation Analysis Using Waist Circumference.

Chronic low-grade inflammation (CLI) is implicated in the development of multiple metabolic diseases. The gut microbiota (GM) activates different signaling pathways and induces phenotypic changes, offering an exciting opportunity to treat CLI. We evaluated the mediation of waist circumference on the association of GM with serum cytokines. In this cross-sectional study of 331 children, we measured 5 gut bacterial species, namely, Lactobacillus (L.) casei, L. paracasei, L. reuteri, Staphylococcus (S.) aureus, and Akkermansia (A.) muciniphila, as well as anthropometry, serum cytokines, and other covariates. We evaluated adjusted regression models, path analysis, and structural equation modeling to obtain path coefficients (PCs) for direct, indirect (waist circumference-mediated), and total effects. We found that L. paracasei was directly associated with lower interleukin-10 (IL-10) levels (PC = -173.5 pg/mL). We also observed indirect associations between S. aureus with lower adiponectin levels (PC = -0.1 µg/mL and -0.09 µg/mL). Finally, A. muciniphila was indirectly associated with higher adiponectin levels (PC = 0.1 µg/mL). Our findings suggest the importance of considering the GM composition and waist circumference when evaluating inflammatory-related factors, providing a basis for future research to identify potential strategies to intervene in inflammatory processes and prevent metabolic diseases in childhood. [Figure: see text].

The Effect of Ultrasound on the Extraction and Functionality of Proteins from Duckweed (Lemna minor).

The inclusion of protein in the regular human diet is important for the prevention of several chronic diseases. In the search for novel alternative protein sources, plant-based proteins are widely explored from a sustainable and ecological point of view. Duckweed (Lemna minor), also known as water lentil, is an aquatic plant with potential applications for human consumption due to its protein content and carbohydrate contents. Among all the conventional and novel protein extraction methods, the utilization of ultrasound has attracted the attention of scientists because of its effects on improving protein extraction and its functionalities. In this work, a Box-Behnken experimental design was proposed to optimize the alkaline extraction of protein from duckweed. In addition, an exploration of the effects of ultrasound on the morphological, structural, and functional properties of the extracted protein was also addressed. The optimal extraction parameters were a pH of 11.5 and an ultrasound amplitude and processing time of 60% and 20 min, respectively. These process conditions doubled the protein content extracted in comparison to the value from the initial duckweed sample. Furthermore, the application of ultrasound during the extraction of protein generated changes in the FTIR spectra, color, and structure of the duckweed protein, which resulted in improvements in its solubility, emulsifying properties, and foaming capacity.

Axial-equatorial equilibrium in substituted cyclohexanes: a DFT perspective on a small but complex problem.

In Chemistry, complexity is not necessarily associated to large systems, as illustrated by the textbook example of axial-equatorial equilibrium in mono-substituted cyclohexanes. The difficulty in modelling such a simple isomerization is related to the need for reproducing the delicate balance between two forces, with opposite effects, namely the attractive London dispersion and the repulsive steric interactions. Such balance is a stimulating challenge for density-functional approximations and it is systematically explored here by considering 20 mono-substituted cyclohexanes. In comparison to highly accurate CCSD(T) reference calculations, their axial-equatorial equilibrium is studied with a large set of 48 exchange-correlation approximations, spanning from semilocal to hybrid to more recent double hybrid functionals. This dataset, called SAV20 (as Steric A-values for 20 molecules), allows to highlight the difficulties encountered by common and more original DFT approaches, including those corrected for dispersion with empirical potentials, the 6-31G*-ACP model, and our cost-effective PBE-QIDH/DH-SVPD protocol, in modeling these challenging interactions. Interestingly, the performance of the approaches considered in this contribution on the SAV20 dataset does not correlate with that obtained with other more standard datasets, such as S66, IDISP or NC15, thus indicating that SAV20 covers physicochemical features not already considered in previous noncovalent interaction benchmarks.

Evolution of the impact of the COVID-19 pandemic on heart transplant recipients: Decreasing risk, improving perspective.

BACKGROUND AND METHODS: Heart transplant recipients (HTr) have a higher probability of suffer from severe coronavirus disease-2019 (COVID-19) in comparison to general population, but their risk has changed over the course of the pandemic in relation to various factors. We conducted a prospective study including all HTr at risk of COVID-19 in a tertiary center between February 2020 and October 2022. The aim was to analyze how the prognosis (incidence of pneumonia and mortality) of COVID-19 in HTr has evolved over time, contextualizing variants, vaccination, and other treatments. RESULTS: Of 308 HTr included, 124 got the infection (39.2%). COVID and non-COVID HTr had similar baseline characteristics. COVID-19 patients with pneumonia had a poorer prognosis than those with less severe presentations, with a higher rate of hospitalization (93.3 vs. 14.1%, p < .001) and death (41.0 vs. 1.2%, p < .001). Multivariate analysis identified age ≥60 years (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.16-11.49, p = .027), and chronic kidney disease ≥3a (OR 4.95, 95% CI 1.39-17.54, p = .014) as predictors of pneumonia. Two-dose vaccination (OR 0.20, CI 95% 0.05-0.72, p = .02) and early remdesivir administration (OR 0.17, CI 0.03-0.90, p = .037) were protective factors. Over the course of the pandemic considering three periods in the follow-up (prevaccination February-December 2020, postvaccination January-December 2021, and post early remdesivir indication January-October 2022), we observed a reduction in pneumonia incidence from 62% to 19% (p < .001); and mortality (from 23% to 4%, p < .001). CONCLUSIONS: The prognosis of COVID-19 in HTr has improved over time, likely due to vaccination and early administration of remdesivir.

Systematic Reviews and Synthesis without Meta-Analysis on Hydrotherapy for Pain Control in Labor.

BACKGROUND: Although there is scientific evidence regarding the use of water immersion during labor, this evidence is primarily focused on the first stage of labor. There is limited scientific evidence on water immersion during the second stage of labor. OBJECTIVE: The objective of this study was to conduct a comprehensive systematic review and synthesis of contemporary evidence related to water birth, with a specific focus on the second stage of labor. METHODS: A systematic review of the scientific literature published between January 2018 and October 2023 was carried out. A synthesis of the results was conducted following the Synthesis without Meta-Analysis (SWiM) guidelines. PubMed, Scopus, and the Cochrane Library were utilized as information sources. The search strategy was designed using the keywords "immersion" and "parturition", along with their relevant synonyms. Inclusion criteria encompassed studies employing randomized controlled trials (RCTs), systematic reviews, and quantitative and qualitative approaches focusing on pregnant women undergoing water immersion at any stage of the labor process. RESULTS: Eleven articles were selected: two systematic reviews (one quantitative and one qualitative), five cohort studies, one case-control study, one cross-sectional observational study, and two qualitative studies. A thorough assessment of the methodology was performed using several specific tools: the Cochrane RoB 2 (Risk of Bias 2) tool for systematic reviews, JBI Critical Appraisal Checklist for Qualitative Research for qualitative studies, STROBE for observational descriptive studies, and CASPe for qualitative studies. The results provided fundamental insights that will contribute to conceptual standardization regarding the effects of water birth on maternal and fetal health. Additionally, a synthesis of the results was performed concerning types of delivery, analgesia use, pain perception, and maternal satisfaction with the water birth experience. CONCLUSIONS: In this study, we conclude that the results regarding delivery types, labor durations, and analgesia use found in the literature, along with statistically significant maternal/fetal effects, are crucial for making recommendations regarding the use of water during labor in any of its stages if the woman desires it safely.

Técnicas complementarias de relajación y analgesia no farmacológicas durante el parto: revisión sistemática / Complementary techniques of relaxation and non-pharmacological analgesia during childbirth: systematic review

Introducción: Existe la necesidad de proporcionar estrategias de analgesia que alienten y promuevan la participación de la mujer en la toma de decisiones en el momento del parto y las técnicas de relajación podrían ser un método analgésico no far-macológico complementario y/o alternativo a la anestesia epidural ampliamente utilizado. en la estándar atención del trabajo de parto. Objetivo: El objetivode este estudio es analizar los efectos obstétricos de las técnicas de relajación en el manejo del dolor durante el parto. Método: Se realiza una revisión sistemática con lectura crítica de los estudios incluidos. La búsqueda de estudios se realizó en las principales bases de datos MEDLINE, Cochrane Library, Cuiden, LILACS y SciELO. Se incluyen estudios publicados en inglés o español entre 2015 y febrero de 2021. Se incluyen una vez estudios, seis de los cuales son revisados sistemáticamente y cinco son ensayos clínicos aleatorios. Las intervenciones analizadas fueron técnicas de relajación como hipnosis, inyección intradérmica de agua estéril, inmersión en agua tibia, masaje, acu-puntura, musicoterapia, aromaterapia, apoyo continuo y prácticas mente-cuerpo como respiración relajante, yoga y meditación, entre otras. Conclusión: La principal conclusión de este estudio es que las técnicas de relajación pueden disminuir el nivel de dolor durante el trabajo, aunque la evidencia científica actual es limitada y la calidad metodológica varía de baja a moderada. Se necesitan más ensayos controlados aleatorios para apoyar esta investigación (AU)

Introduction:There is a need to provide analgesia strategies that encourage and promote women's participation in decision-making at the time of delivery and relaxation techniques could be a complementary and/or alternative non-pharmacological analgesic method to the widely used epidural anaesthesia in standard labour care. Objective: Theobjective of this study is to analyze the obstetric effects of relaxation techniques on pain management during labour. Method: A systematic review is performed with critical reading of included studies. The search for studies was carried out in the main databases MEDLINE, Cochrane Library, Cuiden, LILACS and SciELO. Studies published in English or Spanish between 2015 and February 2021 were included. Eleven studies were included, six of which are systematic reviews and five are randomised clinical trials. The interventions analysed were relaxation techniques such as hypnosis, intradermal injection of sterile water, warm water immersion, massage, acupuncture, music therapy, aromatherapy, continuous support and mind-body practices like relaxing breathing, yoga and meditation, among others. Conclusion: The main conclusion of this study is that relaxation techniques may decrease the level of pain during labour, although the current scientific evidence is limited and the methodological quality varies from low to moderate. More randomised controlled trials are needed to support this research (AU)

De Novo Donor-Specific Antibodies after Heart Transplantation: A Comprehensive Guide for Clinicians.

Antibodies directed against donor-specific human leukocyte antigens (HLAs) can be detected de novo after heart transplantation and play a key role in long-term survival. De novo donor-specific antibodies (dnDSAs) have been associated with cardiac allograft vasculopathy, antibody-mediated rejection, and mortality. Advances in detection methods and international guideline recommendations have encouraged the adoption of screening protocols among heart transplant units. However, there is still a lack of consensus about the correct course of action after dnDSA detection. Treatment is usually started when antibody-mediated rejection is present; however, some dnDSAs appear years before graft failure is detected, and at this point, damage may be irreversible. In particular, class II, anti-HLA-DQ, complement binding, and persistent dnDSAs have been associated with worse outcomes. Growing evidence points towards a more aggressive management of dnDSA. For that purpose, better diagnostic tools are needed in order to identify subclinical graft injury. Cardiac magnetic resonance, strain techniques, or coronary physiology parameters could provide valuable information to identify patients at risk. Treatment of dnDSA usually involves plasmapheresis, intravenous immunoglobulin, immunoadsorption, and ritxumab, but the benefit of these therapies is still controversial. Future efforts should focus on establishing effective treatment protocols in order to improve long-term survival of heart transplant recipients.

Physical Exercise and Dietary Supplementation in Middle-Aged and Older Women: A Systematic Review.

With the aging of the population in developed countries, the number of middle-aged and older women is progressively increasing. During this stage, women suffer from a number of signs and symptoms that could be reduced or treated with physical exercise and dietary supplements. The main objective of this study was to analyse the benefits of exercise and dietary supplements during menopause. MATERIALS AND METHODS: A systematic review of the scientific literature was performed according to the PRISMA 2020 protocol, searching the PubMed, Cochrane, Scopus, and WOS databases. Studies that met the inclusion criteria were assessed for methodological quality using the PEDro or AMSTAR-2 scales. RESULTS: The searches yielded a total of 104 results, of which 10 were selected, with methodological quality ranging from fair to excellent. Each article examined the combination of a dietary supplement plan versus a placebo; plus an exercise routine versus another routine or a sedentary lifestyle. The results showed the benefits of combining a nutritional supplementation plan with an exercise routine during menopause. CONCLUSIONS: The practice of weekly strength and endurance exercises, together with the consumption of certain dietary supplements, may be a good resource for coping with menopause in a healthy way.

SOS1-RSX-QIDH: A spin-opposite-scaled range-separated-exchange quadratic-integrand double-hybrid density functional.

We develop and validate the SOS1-RSX-QIDH density functional, a one-parameter spin-opposite-scaled variant of the range-separated-exchange quadratic-integrand double-hybrid (RSX-QIDH) model. By entering into the family of spin-biased double hybrids, this new density functional benefits from an improved computational scaling that rivals with the one of hybrids, still conserving the accuracy of its RSX-QIDH version. As part of the latter family, this density functional is well-adapted to treat molecular systems that are particularly prone to self-interaction errors in their ground and excited states. In particular, we show that the SOS1-RSX-QIDH model is a good compromise to treat ground-state problems dealing with kinetics and has a real added value when applied to the evaluation of the excited-state properties of equilibrium and out-of-equilibrium molecular complexes. Even if spin-biased double hybrids are recognized to strongly underestimate noncovalent interactions, we notice and recommend coupling SOS1-RSX-QIDH with a nonlocal van der Waals potential, a combination that is here proved to compete with the best density-functional approximations currently in use.

Interaction between Akkermansia muciniphila and Diet Is Associated with Proinflammatory Index in School-Aged Children.

BACKGROUND: Imbalance in the intestinal microbiota can lead to chronic low-grade inflammation. Diet may influence this association. In this study, we aimed to evaluate the interaction between Akkermansia muciniphila (A. muciniphila) and dietary patterns using a proinflammatory index. METHODS: We conducted a cross-sectional study with school-aged children. We quantified the relative abundance (RA) of A. muciniphila in feces using a polymerase chain reaction. We collected dietary information through employing a food frequency questionnaire and generated dietary patterns using principal component analysis. We generated a proinflammatory index from serum levels of interleukin-6, interleukin-10, tumor necrosis factor alpha, and adiponectin validated by receptor operating characteristic curves. We evaluated the association between A. muciniphila and the proinflammatory index using logistic regression, including an interaction term with dietary patterns. RESULTS: We found that children with a low RA of A. muciniphila and a high intake of simple carbohydrates and saturated fats had increased odds of being high on the proinflammatory index. However, when the consumption of this dietary pattern is low, children with a low RA of A. muciniphila had decreased odds of being high on the proinflammatory index. CONCLUSIONS: Our results suggest that the simultaneous presence of A. muciniphila and diet have a more significant impact on the presence of being high on the proinflammatory index compared to both factors separately.

[Inflammatory indexes during remission induction of pediatric acute leukemia]. / Índices inflamatorios durante la inducción a la remisión de leucemia aguda pediátrica.

Background: Inflammatory indexes can reflect the severity of serious diseases such as acute leukemia (AL), which is why they can predict mortality. Objective: To evaluate the prognostic value of mortality of inflammatory indexes during the remission induction stage in patients with pediatric AL. Material and methods: Observational, longitudinal, analytical and retrolective study. Patients aged 0 to 17 years, with a recent and confirmed diagnosis of AL, who had basal (at diagnosis, before the start of treatment) and final (at the end of remission induction, or, in the cases of death, during the period prior to this outcome) complete blood count were included. Results: We included 78 patients, 67 with acute lymphoblastic leukemia (ALL), and 11 with acute myeloblastic leukemia (AML), with 11 and 2 deaths, respectively. Regarding ALL, no index showed significant cut-off points to distinguish deaths. Concerning AML, the indices whose cut-off points distinguished the patients who died in the basal measurement, were the monocyte-lymphocyte ratio (MLR) ≥ 3.11 (sensitivity [Se] 100%, specificity [Sp] 66.67%, AUC 0.8333, p 0.03), and, at the final measurement, the neutrophil-lymphocyte ratio (NLR) ≥ 1.30 and MLR ≥ 0.57 (both with Se 100% and Sp 88.89%, AUC 1.0, p < 0.00001) and systemic immune index (SII) ≥ 246612 (Se 100%, Sp 88.89%, AUC 0.9444, p < 0.0001). With bivariate analysis, only the latter demonstrated an increase in the risk of mortality (p = 0.02). Conclusions: The basal MLR and the final NLR, MLR and SII are prognostic inflammatory indices of mortality in patients with AML undergoing remission induction.

Introducción: los índices inflamatorios pueden reflejar la severidad de padecimientos graves como la leucemia aguda (LA), con lo que pueden predecir la mortalidad. Objetivo: evaluar el valor pronóstico de mortalidad de los índices inflamatorios durante la etapa de inducción a la remisión en pacientes con LA pediátrica. Material y métodos: estudio observacional, longitudinal, analítico y retrolectivo. Se incluyeron pacientes de 0 a 17 años, con diagnóstico reciente y confirmado de LA, que contaron con citometría hemática basal (al diagnóstico, antes del inicio de tratamiento) y final (al término de la inducción a la remisión o en los casos de defunción, en el periodo previo a este desenlace). Resultados: incluimos 78 pacientes, 67 con leucemia linfoblástica aguda (LLA) y 11 con leucemia mieloblástica aguda (LMA), con 11 y 2 defunciones, respectivamente. En la LLA ningún índice mostró puntos de corte significativos para distinguir muertes. En la LMA, los índices cuyos puntos de corte distinguieron a los pacientes que fallecieron en la medición basal fueron el índice monocito linfocito (IML) ≥ 3.11 (sensibilidad [S] 100%, especificidad [E] 66.67%, AUC 0.8333, p 0.03) y en la medición final, el índice neutrófilo linfocito (INL) ≥ 1.30 y el IML ≥ 0.57 (ambos con S 100% y E 88.89%, AUC 1.0, p < 0.00001) y el índice inmunosistémico (IIS) ≥ 246612 (S 100%, E 88.89%, AUC 0.9444, p < 0.0001). Con análisis bivariado solo este último mostró incremento del riesgo de mortalidad (p = 0.02). Conclusiones: el IML basal y el INL, IML e IIS finales son índices inflamatorios pronósticos de mortalidad en pacientes con LMA en inducción a la remisión.

Computational Design of Multiple Resonance-Type BN Molecules for Inverted Singlet and Triplet Excited States.

A computational design of linearly extended multiple resonance (MR)-type BN molecules based on DABNA-1 is proposed herein in the quest to find potential candidates that exhibit a negative singlet-triplet gap (ΔEST) and a large oscillator strength value. The impact of a proper account of the electron correlation in the lowest singlet and triplet excited states is systematically investigated by using double-hybrid functionals within the TD-DFT framework, as well as wavefunction-based methods (EOM-CCSD and SCS-CC2), since this contribution plays an essential role in driving the magnitude of the ΔEST in MR-TADF and inverted singlet-triplet gap compounds. Our results point out a gradual reduction of the ΔEST gap with respect to the increasing sum of the number of B and N atoms, reaching negative ΔEST values for some molecules as a function of their size. The double-hybrid functionals reproduce the gap with only slight deviation compared to available experimental data for DABNA-1, ν-DABNA, and mDBCz and nicely agree with high-level quantum mechanical methods (e.g., EOM-CCSD and SCS-CC2). Larger oscillator strengths are found compared to the azaphenalene-type molecules, also exhibiting the inversion of their singlet and triplet excited states. We hope this study can serve as a motivation for further design of the molecules showing negative ΔEST based on boron- and nitrogen-doped polyaromatic hydrocarbons.

Long COVID and Physical Therapy: A Systematic Review.

Prolonged COVID is a persistent condition following the initial COVID-19 infection, which is characterized by a variety of symptoms that may include fatigue, muscle pain, sleep disturbances, "brain fog", respiratory, cardiovascular, digestive, neurological and dermatological symptoms. Physical therapy has been identified as a crucial aspect of the management of patients with long COVID, as it can help improve symptoms and overall physical function. The investigation of long COVID poses significant challenges due to the diversity and variability of symptoms, lack of clear diagnostic criteria, and limited understanding of the underlying mechanisms. The aim of this study is to conduct a systematic review of studies conducted in patients with long COVID in conjunction with interventions targeting respiratory function, particularly involving physical activity. To this end, we conducted a systematic review to analyze studies conducted on treatment programs for long COVID based on some form of physical activity. The protocol of the review was registered in the PROSPERO website, and the databases PubMed, Scopus, CINAHL and WOS were searched. Of the 62 initial articles, six were included in the review. The results obtained have positive implications for the advancement of physical activity as a therapeutic intervention for individuals with long COVID-19 and the conceptualization of evidence-based treatment protocols. Statistically significant results have been observed in studies of at least 6 weeks duration, in which inspiratory muscle training exercises are proposed. Further research is needed to better understand long COVID and develop effective treatment strategies.

Total neoadjuvant therapy approach for the treatment of locally advanced rectal cancer. Where do we stand?

BACKGROUND: for the management of locally advanced rectal cancer (LARC), initial treatment with neoadjuvant chemoradiotherapy followed by surgery and chemotherapy in selected patients is considered one of the recommended options by the main international clinical guidelines. Nonetheless, the administration of all chemotherapy before definitive treatment (total neoadjuvant therapy or TNT) is an optimal alternative with a growing level of evidence that must be evaluated in multidisciplinary boards. This review summarizes the available data and controversies in this scenario. SUMMARY: we have analyzed the characteristics of the main published studies that assess the use of TNT in patients with LARC, evaluating their inclusion criteria and distinguishing between the employed radiotherapy fractionations, systemic agents, timing, and the implications of these treatments in regard to surgery and long-term oncological results. Our aim is to describe the evidence that supports the use of a specific regime in everyday clinical practice. KEY POINTS: there is solid evidence for the use of TNT in patients with LARC. There is no data indicating the superiority of one specific TNT scheme among all the existing options. International clinical guidelines leave the door open to choose the most adequate treatment based on the clinical and pathological characteristics of each patient. This review shows the different approaches to TNT and assesses the best options based on clinical evidence.

Chiari Syndrome: Advances in Epidemiology and Pathogenesis: A Systematic Review.

Arnold Chiari syndrome is a rare congenital disease of unknown prevalence and whose origin is still under study. It is encompassed within the posterior cranial malformations, showing a wide spectrum of symptomatology that can range from severe headache, dizziness, and paresthesia to complete asymptomatology. It is for this reason that early diagnosis of the disease is difficult, and it is usually diagnosed in adolescence. Treatment is based on remodeling and decompression of the malformed posterior cranial fossa, although the risk of residual symptoms after surgery is high. The aim of this review is to update all the existing information on this pathology by means of an exhaustive analysis covering all the scientific literature produced in the last 5 years. In addition, it has been carried out following the PRISMA model and registered in PROSPERO with code CRD42023394490. One of the main conclusions based on the results obtained in this review is that the origin of the syndrome could have a genetic basis and that the treatment of choice is the decompression of the posterior cerebral fossa.

Safety and Effect of the Use of Hydrotherapy during Labour: A Retrospective Observational Study.

BACKGROUND: Hydrotherapy is a technique used for pain management during labour, but its safety for both the mother and foetus remains uncertain. OBJECTIVE: The main aim of this study is to determine whether the use of hydrotherapy in the first stage of labour is safe for both the mother and newborn. METHODS: A retrospective observational study was conducted to collect data from the partogram, maternal and neonatal history. RESULTS: A total of 377 women who gave birth at the Costa del Sol Hospital in Malaga between January 2010 and December 2020 were randomly selected. They were divided into a control group (253 women) and an intervention group (124 women) that used hydrotherapy in the first stage of labour. There were no significant differences between the groups in terms of age, history of previous miscarriages, type of delivery, or newborn weight. The results showed that most women who opted for hydrotherapy were nulliparous, and the use of hydrotherapy during labour was safe for both the mother and foetus. There were no significant differences in the variables of maternal arterial hypotension, postpartum haemorrhage, postpartum maternal fever, foetal complications, neonatal admission, 1 and 5 min Apgar scores, umbilical arterial or venous pH, or foetal cardiotocographic recording. However, there was a significant difference (p = 0.005) in the rate of breastfeeding among mothers who opted for hydrotherapy (96% vs. 85.7%). CONCLUSIONS: The use of hydrotherapy during the first stage of labour is safe and is associated with increased breastfeeding rates compared to conventional delivery.

RPA, an Accurate and Fast Method for the Computation of Static Nonlinear Optical Properties.

The accurate computation of static nonlinear optical properties (SNLOPs) in large polymers requires accounting for electronic correlation effects with a reasonable computational cost. The Random Phase Approximation (RPA) used in the adiabatic connection fluctuation theorem is known to be a reliable and cost-effective method to render electronic correlation effects when combined with density-fitting techniques and integration over imaginary frequencies. We explore the ability of the RPA energy expression to predict SNLOPs by evaluating RPA electronic energies in the presence of finite electric fields to obtain (using the finite difference method) static polarizabilities and hyperpolarizabilities. We show that the RPA based on hybrid functional self-consistent field calculations yields accurate SNLOPs as the best-tuned double-hybrid functionals developed today, with the additional advantage that the RPA avoids any system-specific adjustment.