The use of healthcare services and disabling chronic pain: results from the cross-sectional population-based Andalusian Health Survey.

BACKGROUND: Several factors seem to be related to the use of healthcare services, and chronic pain (CP) is among these characteristics. The objective is to describe the number of visits to a doctor's surgery or emergency rooms, and the periods of hospitalization; to identify characteristics associated with frequent healthcare use, including disabling chronic pain (DCP) and non-disabling chronic pain (n-DCP). METHODS: Representative population-based cross-sectional study of 6569 people older than 16 years from southern Spain was collected. The frequency of visits to a doctor's surgery or emergency rooms and periods of hospitalization were defined as at or above the 90th percentile. Binary logistic regression analyses were conducted separately on women and men to identify characteristics associated with being frequent visitors. RESULTS: People with DCP are more frequent visitors to a doctor's surgery and emergency rooms and endure longer periods of hospitalization compared to people with n-DCP and without pain. In logistic regression models, people with DCP are twice as likely to over-visit a doctor's surgery; to endure longer periods of hospitalization and more visits to an emergency room service. No relationship was found in n-DCP. CONCLUSIONS: Disability seems to modulate a greater use of health services among the population with CP, doubling it when compared to n-DCP and n-CP, both in women and men. Understanding the role of disability in the use of healthcare services for individuals with CP allows for the identification of needs and strategies to optimize resources.

Novel pentafluorosulfanyl-containing triclocarban analogs selectively kill Gram-positive bacteria.

Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds' activity. Safety profiles were assessed using cytotoxicity experiments in eukaryotic cell lines. Following screening, selected components had significantly better antibacterial and antibiofilm activity against Gram-positive bacteria in lower concentrations in comparison to ciprofloxacin and gentamycin. For instance, one compound had a minimum inhibitory concentration of <0.0003 mM, but ciprofloxacin had 0.08 mM. Mechanistic studies show that these novel compounds do not affect reduced thiol content, iron-sulfur clusters, or hydrogen peroxide pathways. Their impact comes from Gram-positive bacterial cell membrane damage. Tests on cell culture toxicity and host component safety showed promise. Novel diarylurea compounds show promise as Gram-positive antimicrobials. These compounds offer prospects for study and optimization. IMPORTANCE: The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.

Understanding the Impact of Chronic Non-Cancer Pain on Daily Life from a Gender Perspective Using the PAIN_Integral Scale©.

The experience of chronic non-cancer pain differs between women and men due to gender-related factors. This study (1) assessed the difference in responses to the impact of chronic non-cancer pain on daily life in women and men using the PAIN_Integral Scale© and (2) evaluated its invariance through multigroup confirmatory factor analysis. This was conducted by means of an analysis of invariance through a multigroup confirmatory factor analysis. A cross-sectional sample of 400 participants over 18 years of age with Chronic Non-Oncological Pain in Pain Units and Primary Care Centres belonging to the Spanish Public Health System was recruited (January to March 2020). An analysis was performed to assess whether any of the items in the instrument showed different behaviours. All analyses were performed using AMOS® v.26 software. The results showed that the structure of the PAIN_Integral© Scale remained adequate when analysing its invariance in women and men, showing no metric, scalar and/or strict invariance. Therefore, these results indicated that the PAIN_Integral Scale© instrument has a different interpretation for women and men, identifying eight items with a singular functioning in both sexes and belonging to the subscales of proactivity, resilience and support network. These findings can be explained by gender stereotypes, since the dimensions where there are differences have an important social burden.

A rare case of Salmonella-associated acute pancreatitis in a patient with ulcerative colitis.

Inflammatory bowel disease is a known risk factor for enteric infections such as Salmonella. This infection can affect almost all major organs. Acute Salmonella pancreatitis is a rare complication. This is the case of a 61-year-old man with ulcerative colitis who developed acute pancreatitis complicating Salmonella infection.

Ozone responses to reduced precursor emissions: A modeling analysis on how attainable goals can improve air quality in the Mexico City Metropolitan Area.

High tropospheric ozone (O3) concentrations prevent the improvement of the air quality in the Mexico City Metropolitan Area (MCMA). Although the problem has improved considerably since the 1990s, a rebound in O3 levels in recent years has raised concerns about the deteriorating air quality. The nonlinear relationship between O3 formation and the emissions of its main precursors, i.e., volatile organic compounds (VOCs) and nitrogen oxides (NOx), is a challenge when measures are enacted for effective mitigation of the O3 problem. This study evaluated the reduction in precursors, VOCs and NOx, using an up-to-date regional air quality model (HERMES-Mex-WRF-CMAQ). For evaluating realizable scenarios, the decline in VOC achieved in Japan after policy implementation was the targeted VOC reduction (40 % from area sources), and the NOx reduction observed in the MCMA during the COVID-19 pandemic was the targeted NOx reduction (40 % from mobile sources). The analysis evaluated the O3 responses to changes in a single precursor and a combination of both during a period of high O3 concentrations (April 2019). The results showed that 40 % reduction in VOC emissions would decrease the O3 8-h maximum concentrations by 16 %. However, 40 % reduction in NOx emissions would increase O3 by >15 %. The simultaneous reduction of both precursors did not significantly affect O3 levels. The diagnosis of ozone sensitivity using the H2O2/HNO3 ratios reinforced the simulation findings, indicating that VOC emissions limited ozone formation in most MCMA areas. As the simulated scenarios were based on factual case studies, our research offers insights into the realistic aims of MCMA policies to reduce O3 levels.

Novel molecular mechanism driving neuroprotection after soluble epoxide hydrolase inhibition: Insights for Alzheimer's disease therapeutics.

BACKGROUND: Neuroinflammation is widely recognized as a significant hallmark of Alzheimer's disease (AD). To combat neuroinflammation, the inhibition of the soluble epoxide hydrolase (sEH) enzyme has been demonstrated crucial. Importantly, sEH inhibition could be related to other neuroprotective pathways described in AD. AIMS: The aim of the study was to unveil new molecular pathways driving neuroprotection through sEH, we used an optimized, potent, and selective sEH inhibitor (sEHi, UB-SCG-51). MATERIALS AND METHODS: UB-SCG-51 was tested in neuroblastoma cell line, SH-SY5Y, in primary mouse and human astrocytes cultures challenged with proinflammatory insults and in microglia cultures treated with amyloid oligomers, as well as in mice AD model (5XFAD). RESULTS: UB-SCG-51 (10 and 30 µM) prevented neurotoxic reactive-astrocyte conversion in primary mouse astrocytes challenged with TNF-α, IL-1α, and C1q (T/I/C) combination for 24 h. Moreover, in microglial cultures, sEHi reduced inflammation and glial activity. In addition, UB-SCG-51 rescued 5XFAD cognitive impairment, reducing the number of Amyloid-ß plaques and Tau hyperphosphorylation accompanied by a reduction in neuroinflammation and apoptotic markers. Notably, a transcriptional profile analysis revealed a new pathway modulated by sEHi treatment. Specifically, the eIF2α/CHOP pathway, which promoted the endoplasmic reticulum response, was increased in the 5XFAD-treated group. These findings were confirmed in human primary astrocytes by combining sEHi and eIF2α inhibitor (eIF2αi) treatment. Besides, combining both treatments resulted in increased in C3 gene expression after T/I/C compared with the group treated with sEHi alone in cultures. DISCUSSION: Therefore, sEHi rescued cognitive impairment and neurodegeneration in AD mice model, based on the reduction of inflammation and eIF2α/CHOP signaling pathway. CONCLUSIONS: In whole, our results support the concept that targeting neuroinflammation through sEH inhibition is a promising therapeutic strategy to fight against Alzheimer's disease with additive and/or synergistic activities targeting neuroinflammation and cell stress.

Tobacco Mild Green Mosaic Virus (TMGMV) Isolates from Different Plant Families Show No Evidence of Differential Adaptation to Their Host of Origin.

The relevance of tobamoviruses to crop production is increasing due to new emergences, which cannot be understood without knowledge of the tobamovirus host range and host specificity. Recent analyses of tobamovirus occurrence in different plant communities have shown unsuspectedly large host ranges. This was the case of the tobacco mild green mosaic virus (TMGMV), which previously was most associated with solanaceous hosts. We addressed two hypotheses concerning TMGMV host range evolution: (i) ecological fitting, rather than genome evolution, determines TMGMV host range, and (ii) isolates are adapted to the host of origin. We obtained TMGMV isolates from non-solanaceous hosts and we tested the capacity of genetically closely related TMGMV isolates from three host families to infect and multiply in 10 hosts of six families. All isolates systemically infected all hosts, with clear disease symptoms apparent only in solanaceous hosts. TMGMV multiplication depended on the assayed host but not on the isolate's host of origin, with all isolates accumulating to the highest levels in Nicotiana tabacum. Thus, results support that TMGMV isolates are adapted to hosts in the genus Nicotiana, consistent with a well-known old virus-host association. In addition, phenotypic plasticity allows Nicotiana-adapted TMGMV genotypes to infect a large range of hosts, as encountered according to plant community composition and transmission dynamics.

Soluble epoxide hydrolase-targeting PROTAC activates AMPK and inhibits endoplasmic reticulum stress.

Soluble epoxide hydrolase (sEH) is a drug target with the potential for therapeutic utility in the areas of inflammation, neurodegenerative disease, chronic pain, and diabetes, among others. Proteolysis-targeting chimeras (PROTACs) molecules offer new opportunities for targeting sEH, due to its capacity to induce its degradation. Here, we describe that the new ALT-PG2, a PROTAC that degrades sEH protein in the human hepatic Huh-7 cell line, in isolated mouse primary hepatocytes, and in the liver of mice. Remarkably, sEH degradation caused by ALT-PG2 was accompanied by an increase in the phosphorylated levels of AMP-activated protein kinase (AMPK), while phosphorylated extracellular-signal-regulated kinase 1/2 (ERK1/2) was reduced. Consistent with the key role of these kinases on endoplasmic reticulum (ER) stress, ALT-PG2 attenuated the levels of ER stress and inflammatory markers. Overall, the findings of this study indicate that targeting sEH with degraders is a promising pharmacological strategy to promote AMPK activation and to reduce ER stress and inflammation.

Endoscopic Vacuum Therapy for Upper Gastrointestinal Leaks and Perforations: Analysis From a Multicenter Spanish Registry.

INTRODUCTION: Endoscopic vacuum therapy (EVT) is a novel technique for closing upper gastrointestinal (UGI) defects. Available literature includes single-center retrospective cohort studies with small sample sizes. Furthermore, evidence about factors associated with EVT failure is scarce. We aimed to assess the efficacy and safety of EVT for the resolution of UGI defects in a multicenter study and to investigate the factors associated with EVT failure and in-hospital mortality. METHODS: This is a prospective cohort study in which consecutive EVT procedures for the treatment of UGI defects from 19 Spanish hospitals were recorded in the national registry between November 2018 and March 2022. RESULTS: We included 102 patients: 89 with anastomotic leaks and 13 with perforations. Closure of the defect was achieved in 84 cases (82%). A total of 6 patients (5.9%) had adverse events related to the EVT. The in-hospital mortality rate was 12.7%. A total of 6 patients (5.9%) died because of EVT failure and 1 case (0.9%) due to a fatal adverse event. Time from diagnosis of the defect to initiation of EVT was the only independent predictor for EVT failure (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, P = 0.005). EVT failure (OR 24.5, 95% CI 4.5-133, P = 0.001) and development of pneumonia after EVT (OR 246.97, 95% CI 11.15-5,472.58, P = 0.0001) were independent predictors of in-hospital mortality. DISCUSSION: EVT is safe and effective in cases of anastomotic leak and perforations of the upper digestive tract. The early use of EVT improves the efficacy of this technique.

Design and Synthesis of AMPK Activators and GDF15 Inducers.

Targeting growth differentiation factor 15 (GDF15) is a recent strategy for the treatment of obesity and type 2 diabetes mellitus (T2DM). Here, we designed, synthesized, and pharmacologically evaluated in vitro a novel series of AMPK activators to upregulate GDF15 levels. These compounds were structurally based on the (1-dibenzylamino-3-phenoxy)propan-2-ol structure of the orphan ubiquitin E3 ligase subunit protein Fbxo48 inhibitor, BC1618. This molecule showed a better potency than metformin, increasing GDF15 mRNA levels in human Huh-7 hepatic cells. Based on BC1618, structural modifications have been performed to create a collection of diversely substituted new molecules. Of the thirty-five new compounds evaluated, compound 21 showed a higher increase in GDF15 mRNA levels compared with BC1618. Metformin, BC1618, and compound 21 increased phosphorylated AMPK, but only 21 increased GDF15 protein levels. Overall, these findings indicate that 21 has a unique capacity to increase GDF15 protein levels in human hepatic cells compared with metformin and BC1618.

Leadership in a hospital of the Andalusian Public Health System.

OBJECTIVE: To analyse, from a gender perspective, the characteristics and perception of the effects of leadership of nurses in a hospital of the Andalusian Public Health System. METHODOLOGY: Qualitative study with a phenomenological approach. The participants were nurses in care and intermediate positions with a contract of more than 6 months. A qualitative content analysis was carried out. Four phases were established for data analysis, from which 5 categories resulted. NVivo 11 software was used to analyse the dialogues. RESULTS: The participants' discourses endow the leader with characteristics that define him as a reference person. The contribution of middle management is necessary for the achievement of the objectives of the care units and the cohesion of the group, although this group perceives it only in relation to the management of resources. Access to management positions is not linked to gender. CONCLUSIONS: The participants' discourses endow the leader with characteristics that define him as a reference person. The contribution of middle management is necessary for the achievement of the objectives of the care units and the cohesion of the group, although this group perceives it only in relation to the management of resources. Access to management positions is not linked to gender.

A Study of the Activity of Adamantyl Amines against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple Blocker, Explored by Molecular Dynamics Simulations and Solid-State NMR.

We compared the anti-influenza potencies of 57 adamantyl amines and analogs against influenza A virus with serine-31 M2 proton channel, usually termed as WT M2 channel, which is amantadine sensitive. We also tested a subset of these compounds against viruses with the amantadine-resistant L26F, V27A, A30T, G34E M2 mutant channels. Four compounds inhibited WT M2 virus in vitro with mid-nanomolar potency, with 27 compounds showing sub-micromolar to low micromolar potency. Several compounds inhibited L26F M2 virus in vitro with sub-micromolar to low micromolar potency, but only three compounds blocked L26F M2-mediated proton current as determined by electrophysiology (EP). One compound was found to be a triple blocker of WT, L26F, V27A M2 channels by EP assays, but did not inhibit V27A M2 virus in vitro, and one compound inhibited WT, L26F, V27A M2 in vitro without blocking V27A M2 channel. One compound blocked only L26F M2 channel by EP, but did not inhibit virus replication. The triple blocker compound is as long as rimantadine, but could bind and block V27A M2 channel due to its larger girth as revealed by molecular dynamics simulations, while MAS NMR informed on the interaction of the compound with M2(18-60) WT or L26F or V27A.

A slightly different polyp: melanoma metastasis diagnosed by colonoscopy.

Melanoma metastases are rare in the colon. Its diagnosis is difficult because they do not usually produce symptoms. They can present through the endoscopic image of a non-pigmented polyp. This is the case of a 56-year-old woman diagnosed with melanoma metastasis through polypectomy of an unusual-looking polyp.

Synthesis and Testing of Analogs of the Tuberculosis Drug Candidate SQ109 against Bacteria and Protozoa: Identification of Lead Compounds against Mycobacterium abscessus and Malaria Parasites.

SQ109 is a tuberculosis drug candidate that has high potency against Mycobacterium tuberculosis and is thought to function at least in part by blocking cell wall biosynthesis by inhibiting the MmpL3 transporter. It also has activity against bacteria and protozoan parasites that lack MmpL3, where it can act as an uncoupler, targeting lipid membranes and Ca2+ homeostasis. Here, we synthesized 18 analogs of SQ109 and tested them against M. smegmatis, M. tuberculosis, M. abscessus, Bacillus subtilis, and Escherichia coli, as well as against the protozoan parasites Trypanosoma brucei, T. cruzi, Leishmania donovani, L. mexicana, and Plasmodium falciparum. Activity against the mycobacteria was generally less than with SQ109 and was reduced by increasing the size of the alkyl adduct, but two analogs were ∼4-8-fold more active than SQ109 against M. abscessus, including a highly drug-resistant strain harboring an A309P mutation in MmpL3. There was also better activity than found with SQ109 with other bacteria and protozoa. Of particular interest, we found that the adamantyl C-2 ethyl, butyl, phenyl, and benzyl analogs had 4-10× increased activity against P. falciparum asexual blood stages, together with low toxicity to a human HepG2 cell line, making them of interest as new antimalarial drug leads. We also used surface plasmon resonance to investigate the binding of inhibitors to MmpL3 and differential scanning calorimetry to investigate binding to lipid membranes. There was no correlation between MmpL3 binding and M. tuberculosis or M. smegmatis cell activity, suggesting that MmpL3 is not a major target in mycobacteria. However, some of the more active species decreased lipid phase transition temperatures, indicating increased accumulation in membranes, which is expected to lead to enhanced uncoupler activity.

Evaluation of adherence monitoring in buprenorphine treatment: A pilot study using timed drug assays to determine accuracy of testing.

AIMS: Buprenorphine is effective at reducing relapse to opioid misuse, morbidity and mortality in opioid-dependent patients. Urine drug screening (UDS) to assess adherence is used routinely in opioid agonist treatment (OAT). The primary aim of this study was to determine factors which may be associated with a negative qualitative urine drug screen for buprenorphine in OAT patients. METHODS: This prospective pilot study was conducted at a tertiary addiction medicine centre. Twenty participants on stable treatment underwent supervised administration of sublingual buprenorphine. Matched urine and blood samples were collected prior to and 2, 4 and 6 hours after buprenorphine administration. Qualitative urine drug screen results were obtained using gas chromatography-mass spectrometry (GC-MS), while quantitative blood and urine results were obtained using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: Qualitative urine assay yielded a negative result for buprenorphine in 57% of tested samples. The median concentration of urinary buprenorphine was 167 mcg/L (range: 2-1730 mcg/L). Thirty percent of all blood samples did not detect buprenorphine (range 0-18 mcg/L). Positive qualitative urine drug screen results were associated with higher urine (343 mcg/L compared with 75 mcg/L; P < .05) and blood (4 mcg/L compared with 2 mcg/L; P < .05) buprenorphine concentrations. Median urine concentrations of buprenorphine were highest at 2 hours and were higher in participants receiving CYP3A4 inhibitors. CONCLUSION: Interpretation of qualitative urine drug screens to assess adherence in OAT is complex. Poor adherence with treatment cannot be assumed in patients returning a negative qualitative GC-MS urine drug screen.

Factors that influence the impact of Chronic Non-Cancer Pain on daily life: A partial least squares modelling approach.

BACKGROUND: Chronic Non-Cancer Pain is pain of more than three months' duration and is not associated with an oncological condition. There is ample literature that recognises that Chronic Non-Cancer Pain impacts numerous areas of the life of the person who suffers from it. This impact is difficult to determine and quantify because Chronic Pain is a subjective experience. OBJECTIVE: The objective of this study was to test a recursive model of hypothesised factors that comprise the concept of Chronic Non-Cancer Pain Impact on daily life using Partial Least Squares-Structural Equation Modelling. DESIGN: A cross-sectional study was carried out. The sample size was calculated using G*Power V.3.1.9.4 with five parameters (two-tailed, large effect size (f2 = 0.35), power of 0.95, statistical significance of 95% (α = 0.05) and 36 predictors). The minimum number of subjects was considered to be 137. METHODS: A recursive model was built based on data from a sample of 395 people over 18 years of age with Chronic Non-Cancer Pain. Data collection was conducted between January and March 2020 at Pain Units and Primary Healthcare Centres belonging to the Spanish Public Health System in the province of Seville (Spain). Analyses were based on Partial Least Squares-Structural Equation Modelling. The internal consistency, convergent validity and discriminant validity of the internal measurement model were assessed. For the external measurement model, global model adjustment and structural validity were assessed. The predictive capacity of the final model was also evaluated. All analyses were performed using SmartPLS version 3.3.2 in consistent mode. RESULTS: Findings showed an adequate validity of the proposed model, which comprised nine factors: pain catastrophising, hopelessness due to pain, support network, proactivity, treatment compliance, self-care, mobility, resilience, and sleep. The internal validity of the model (Cronbach's alpha and rho_A > 0.70; Average Variance Extracted>0.50; standardised outer loadings>0.60; Heterotrait-Monotrait-Ratio < 0.85), goodness of fit (Standardised Root Mean Square Residuals<0.08; Geodesic and Euclidean distance p-value<0.05) and predictive power with out-of-sample values (Stone-Geisser test>0.5) were adequate. The hypothesised structure of the instrument has also been confirmed (path coefficients>0.3; R2 > 0.1; f2 > 0.2). CONCLUSIONS: The results have shown an adequate internal consistency, convergent validity and discriminant validity of the model. Likewise, the model has shown an adequate goodness of fit, and the validity of its structure and the hypothesis have been confirmed. However, more research is needed in this regard as the possible interaction between the different factors evaluated in the model with the confounding or moderating variables that may exist.

Inconmensurabilidad: un obstáculo para la integración de la psicoterapia y la espiritualidad. Los padres del desierto como paradigma epistemológico superador / Incommensurability: An Obstacle to the Integration of Psychotherapy and Spirituality. The Desert Fathers as an Overcoming Epistemological Paradigm

RESUMEN En los últimos arios ha crecido exponencialmente el cuerpo de literatura que se ocupa de ensayar diversas maneras de integrar la espiritualidad en la práctica psicoterapéutica. Probablemente el interés por esta temática haya surgido a propósito de la inclusión en el DSM-IV de la nueva categoría «Problema religioso o espiritual¼ (código V62.89). Hasta entonces las cuestiones religiosas o espirituales habían sido objeto de la clínica en tanto síntomas de algunas enfermedades mentales, como los delirios con contenidos religiosos propios de los esquizofrénicos. Pero con la cuarta edición del citado manual comienza a interesar el estudio de la espiritualidad en tanto que expresa un aspecto fundamental de la personalidad. En esta línea, se han formulado diversos modelos de integración de la espiritualidad y la psicoterapia. Nuestra intención es estudiar el problema de la inconmensurabilidad como uno de los problemas epistemológicos y metodológicos medulares que supone un proyecto de este tipo. Presentamos los escritos de los Padres del desierto como un modelo explicativo que garantiza una integración epistemológicamente legítima de las tradiciones espirituales con la práctica psicoterapéutica. Y por eso mismo argumentamos que sus escritos podrían constituir una vía superadora de la relación de mutua inconmensurabilidad que aparentemente existe entre la racionalidad científica y la espiritualidad.

ABSTRACT In recent years, the body of literature that deals with trying different ways of integrating spirituality into psychotherapeutic practice has grown exponentially. Probably the interest in this topic has arisen with regard to the inclusion in the DSM-IV of the new category "Religious or Spiritual Problem" (Code V62.89). Until then, religious or spiritual issues had been viewed in the clinical practice as symptoms of some mental illnesses like, for example, the delusions with religious content typical of schizophrenics. But with the fourth edition of the aforementioned manual, there began to be an interest in the study of spirituality as it expresses a fundamental aspect of personality. In this vein, various models of integration of spirituality and psychotherapy have been formulated. Our intention is to study the problem of incommensurability as one of the epistemological and methodological problems that supposes a project of this type. We present the writings of the Desert Fathers as an explanatory model that guarantees an epistemologically legitimate integration of spiritual traditions with psychotherapeutic practice. And for that reason, we argue that their writings could constitute a way to overcome the relationship of mutual incommensurability that apparently exists between scientific rationality and spirituality.

Incommensurability: an obstacle to the integration of psychotherapy and spirituality. the desert fathers as an overcoming epistemological paradigm.

In recent years, the body of literature that deals with trying different ways of integrating spirituality into psychotherapeutic practice has grown exponentially. Probably the interest in this topic has arisen with regard to the inclusion in the DSM-IV of the new category "Religious or Spiritual Problem" (Code V62.89). Until then, religious or spiritual issues had been viewed in the clinical practice as symptoms of some mental illnesses like, for example, the delusions with religious content typical of schizophrenics. But with the fourth edition of the aforementioned manual, there began to be an interest in the study of spirituality as it expresses a fundamental aspect of personality. In this vein, various models of integration of spirituality and psychotherapy have been formulated. Our intention is to study the problem of incommensurability as one of the epistemological and methodological problems that supposes a project of this type. We present the writings of the Desert Fathers as an explanatory model that guarantees an epistemologically legitimate integration of spiritual traditions with psychotherapeutic practice. And for that reason, we argue that their writings could constitute a way to overcome the relationship of mutual incommensurability that apparently exists between scientific rationality and spirituality.

Maternal and neonatal immune response to SARS-CoV-2, IgG transplacental transfer and cytokine profile.

SARS-CoV-2 infected pregnant women are at increased risk of severe COVID-19 than non-pregnant women and have a higher risk of adverse pregnancy outcomes like intrauterine/fetal distress and preterm birth. However, little is known about the impact of SARS-CoV-2 infection on maternal and neonatal immunological profiles. In this study, we investigated the inflammatory and humoral responses to SARS-CoV-2 in maternal and cord blood paired samples. Thirty-six pregnant women were recruited at delivery at Hospital Sant Joan de Déu, Barcelona, Spain, between April-August 2020, before having COVID-19 available vaccines. Maternal and pregnancy variables, as well as perinatal outcomes, were recorded in questionnaires. Nasopharyngeal swabs and maternal and cord blood samples were collected for SARS-CoV-2 detection by rRT-PCR and serology, respectively. We measured IgM, IgG and IgA levels to 6 SARS-CoV-2 antigens (spike [S], S1, S2, receptor-binding domain [RBD], nucleocapsid [N] full-length and C-terminus), IgG to N from 4 human coronaviruses (OC43, HKU1, 229E and NL63), and the concentrations of 30 cytokines, chemokines and growth factors by Luminex. Mothers were classified as infected or non-infected based on the rRT-PCR and serology results. Sixty-four % of pregnant women were infected with SARS-CoV-2 (positive by rRT-PCR during the third trimester and/or serology just after delivery). None of the newborns tested positive for rRT-PCR. SARS-CoV-2 infected mothers had increased levels of virus-specific antibodies and several cytokines. Those with symptoms had higher cytokine levels. IFN-α was increased in cord blood from infected mothers, and in cord blood of symptomatic mothers, EGF, FGF, IL-17 and IL-15 were increased, whereas RANTES was decreased. Maternal IgG and cytokine levels showed positive correlations with their counterparts in cord blood. rRT-PCR positive mothers showed lower transfer of SARS-CoV-2-specific IgGs, with a stronger effect when infection was closer to delivery. SARS-CoV-2 infected mothers carrying a male fetus had higher antibody levels and higher EGF, IL-15 and IL-7 concentrations. Our results show that SARS-CoV-2 infection during the third trimester of pregnancy induces a robust antibody and cytokine response at delivery and causes a significant reduction of the SARS-CoV-2-specific IgGs transplacental transfer, with a stronger negative effect when the infection is closer to delivery.

Glial cell reactivity and oxidative stress prevention in Alzheimer's disease mice model by an optimized NMDA receptor antagonist.

In Alzheimer's disease pathology, several neuronal processes are dysregulated by excitotoxicity including neuroinflammation and oxidative stress (OS). New therapeutic agents capable of modulating such processes are needed to foster neuroprotection. Here, the effect of an optimised NMDA receptor antagonist, UB-ALT-EV and memantine, as a gold standard, have been evaluated in 5XFAD mice. Following treatment with UB-ALT-EV, nor memantine, changes in the calcineurin (CaN)/NFAT pathway were detected. UB-ALT-EV increased neurotropic factors (Bdnf, Vgf and Ngf) gene expression. Treatments reduced astrocytic and microglial reactivity as revealed by glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1) quantification. Interestingly, only UB-ALT-EV was able to reduce gene expression of Trem2, a marker of microglial activation and NF-κB. Pro-inflammatory cytokines Il-1ß, Ifn-γ, Ccl2 and Ccl3 were down-regulated in UB-ALT-EV-treated mice but not in memantine-treated mice. Interestingly, the anti-inflammatory markers of the M2-migroglial phenotype, chitinase-like 3 (Ym1) and Arginase-1 (Arg1), were up-regulated after treatment with UB-ALT-EV. Since iNOS gene expression decreased after UB-ALT-EV treatment, a qPCR array containing 84 OS-related genes was performed. We found changes in Il-19, Il-22, Gpx6, Ncf1, Aox1 and Vim gene expression after UB-ALT-EV. Hence, our results reveal a robust effect on neuroinflammation and OS processes after UB-ALT-EV treatment, surpassing the memantine effect in 5XFAD.