Pain Sensitization and Association With Baseline Factors in Elderly Patients With Distal Radius Fracture: A Cross-Sectional Study.

BACKGROUND: The aim of this study was to describe the presence of pain sensitization (PS) and its association with baseline factors after cast removal in patients older than 60 years with distal radius fracture (DRF) treated conservatively. METHODS: This cross-sectional study included 220 patients older than 60 years with extra-articular DRF who completed the Pain Sensitivity Questionnaire (PSQ). Patients with PSQ score > 7 points were considered positive for PS. In addition, sociodemographic, anthropometrics, clinical, radiological, lifestyle behaviors, pain-related psychological factors, and functional outcomes were analyzed as baseline predictors, all measured were performed 2 weeks after cast removal. RESULTS: A total of 159 patients (72.3%) showed PS. The results showed an association between higher values of PSQ-total with the affected dominant hand (ß = 1.1; P = 0.04), high energy of injury (ß = 3.5; P < .001), extra-articular comminuted metaphyseal DRFs (ß = 1.8; P < .001), lower values of Rapid Assessment of Physical Activity questionnaire (ß = 3.1; P < .001), higher values of Pittsburgh Sleep Quality Index (ß = 2.5; P < .001), higher values of Tampa Scale of Kinesiophobia (ß = 1.9; P < .001), higher values of Pain Catastrophizing Scale (ß = 1.8; P < .001), higher values of Disabilities of the Arm, Shoulder and Hand questionnaire (ß = 1.6; P < .001), lower values of grip strength (ß = 1.4; P < .001) and higher values of Visual analog scale (ß = 4.2; P < .001). CONCLUSIONS: A high percentage of patients older than 60 years with extra-articular DRFs present PS at 2 weeks after cast removal. Our results may help physicians and physiotherapists identify risk and/or prognostic baseline factors for the occurrence of PS after DRF, and the need for a therapeutic approach that incorporates the clinical management of this condition in these patients.

Changes in Prevalence of IgE Sensitization and Allergenic Exposition over a 10-Year Period in a Tropical Region.

INTRODUCTION: Multiple antigen environmental sources have been identified as possible causes of allergies, but few studies have evaluated changes in the sensitization profiles over time. The aim of this study was to evaluate the changes in IgE sensitization and exposure to dust mites, cats, dogs, and cockroaches over a 10-year period. METHODS: During a period of 10 years among patients with asthma, rhinitis and/or atopic dermatitis, we evaluated the annual frequency of atopy to Dermatophagoides farinae, Dermatophagoides pteronyssinus, Blomia tropicalis, Canis familiaris, Felis domesticus and cockroaches (Periplaneta americana and Blatella germanica). Exposure to sources was also assessed using questionnaires (Pets) or direct counts (House dust mites and cockroaches). The association between some risk factors and the prevalence of atopy was explored. RESULTS: A total of 6,000 records were included. Among the patients, 82% had IgE sensitization to at least one of the six allergenic sources. Sensitization to Dermatophagoides spp. was the most frequent (>78%). Exposure and sensitization in the first decade of life to Dermatophagoides spp. seem to determine the molecular spreading to other allergenic sources. Exposure to Blomia tropical increases significantly over time (year 2015; 38% vs. year 2022; 51%, p 0.03). Exposure to dogs was higher than with cats but association between atopy and exposure was stronger with cats (OR 27.4, 95% CI: 22.3-33.6, p < 0.01). CONCLUSION: Exposure and sensitization in the first decade of life to Dermatophagoides spp. determine the molecular spreading of IgE antibodies to other allergenic sources. Household exposure to dogs and cats seems to be important for the subsequent development of atopy. Sensitization to B. tropicalis and cockroach appears to be mostly from cross-reactivity rather than direct exposure.

A Pain Desensitization Algorithm for Phenotyping and Treating Chronic Pelvic Pain.

Background: Chronic pelvic pain remains challenging for physicians to manage due to central and peripheral sensitization and multiple pain generators including the bladder, pelvic floor, and pudendal nerve. Pain management providers have used nerve blocks for years for diagnosis and treatment. We developed a desensitization algorithm that provides a stepwise approach to improve patients pain scores. Methods: This is a prospective observational cohort study of 182 women aged 15-90 years old with chronic pelvic pain using an algorithm from 2016 to 2018. Treatment started with an Anesthetic Challenge Test of the bladder to guide us through a protocol of intravesical therapy and/or pudendal nerve blocks as a second step. Results: ACT POSITIVE patients, who received intravesical therapy: 84% had a Visual Analog Score pain improvement of at least 50%, 64% improved at least 80% (41% pain-free). Those desiring additional relief that received further Pudendal Blocks: 83% had final improvement of at least 50% (67% pain-free). ACT NEGATIVE patients received Pudendal Blocks with 80% of subjects achieving at least 50% relief, 65% improved at least 80% (35% pain-free). All final groups showed a statistically significance of P < .05% when compared to their initial pain scores. Conclusion: Management of women with chronic pelvic pain would ideally start with treating a specific diagnosis which, in most cases, is difficult to establish since the majority have more than one pain generator. Our algorithm simplified the approach and reduced the severity of pain scores prior to any further necessary surgical interventions.

Mirtazapine decreased cocaine-induced c-fos expression and dopamine release in rats.

Introduction: Chronic cocaine exposure induces an increase in dopamine release and an increase in the expression of the Fos protein in the rat striatum. It has been suggested that both are necessary for the expression of cocaine-induced alterations in behavior and neural circuitry. Mirtazapine dosing attenuated the cocaine-induced psychomotor and reinforcer effects. Methods: The study evaluates the effect of chronic dosing of mirtazapine on cocaine-induced extracellular dopamine levels and Fos protein expression in rats. Male Wistar rats received cocaine (10 mg/Kg; i.p.) during the induction and expression of locomotor sensitization. The mirtazapine (30 mg/Kg; MIR), was administered 30 minutes before cocaine during the cocaine withdrawal. After each treatment, the locomotor activity was recorded for 30 minutes. Animals were sacrificed after treatment administration. Dopamine levels were determined by high-performance liquid chromatographic (HPLC) in the ventral striatum, the prefrontal cortex (PFC), and the ventral tegmental area (VTA) in animals treated with mirtazapine and cocaine. The quantification of c-fos immunoreactive cells was carried out by stereology analysis. Results: Mirtazapine generated a decrease in cocaine-induced locomotor activity. In addition, mirtazapine decreased the amount of cocaine-induced dopamine and the number of cells immunoreactive to the Fos protein in the striatum, PFC, and VTA. Discussion: These data suggest that mirtazapine could prevent the consolidation of changes in behavior and the cocaine-induced reorganization of neuronal circuits. It would explain the mirtazapine-induced effects on cocaine behavioral sensitization. Thus, these data together could support its possible use for the treatment of patients with cocaine use disorder.

Exploring the role of viscosity-vaso-occlusion and haemolysis-endothelial dysfunction in pain sensitization among Jamaicans with sickle cell disease.

Viscosity-vaso-occlusion (VVO) and haemolysis-endothelial dysfunction (HED) are pathophysiological mechanisms and clinical subphenotypes of sickle cell disease (SCD). Recurrent vaso-occlusive crises (VOC) may lead to neuroplastic changes and pain sensitization. Among 257 SCD participants, we assessed the relationship of subphenotypes with pain sensitivity using quantitative sensory testing to identify heat pain thresholds (HPT) and pressure pain thresholds (PPT). VOC history and sleep, social and emotional functioning were assessed using the Adult Sickle Cell Quality of Life Measurement Information System. The 'elbow method' determined the optimal number of clusters as three. Clustering was performed using K-prototypes. Among clusters 2 and 3, VOC frequency and severity were higher. Clusters 1 and 3 had lower haemoglobin, higher reticulocytes and lactate dehydrogenase and more leg ulcers. In multivariate regression, cluster 3 was associated with approximately 13.6% lower PPT compared to cluster 1, and female sex was associated with decreases in PPT and HPT at the hands and feet (p < 0.001). Hydroxyurea use and unit increases in sleep functioning and age were associated with approximately 20.1% higher foot-PPT, 6.8% higher hand-PPT and 2.5% higher hand-HPT and foot-HPT respectively. Findings suggest that a third subphenotype with mixed VVO and HED features and worse pain sensitization may exist.

Chronic Musculoskeletal Pain and Central Sensitization-Related Symptoms in Chilean Victims of Political Violence During the 1973 to 1990 Dictatorship.

People who suffer political violence (PV) are at risk of developing mental illness, chronic noncommunicable diseases, chronic pain, and decreased life expectancy. However, these indicators have been studied primarily in war veterans and refugees. The objective of this study was to estimate the prevalence of chronic musculoskeletal pain (CMP) and central sensitization-related symptoms (CSRS) in Chilean victims of PV during the 1973 to 1990 dictatorship. A cross-sectional observational multicenter study was conducted. Three hundred twenty-five people from six centers of a Ministry of Health of Chile program participated. The presence of CMP was determined by a history of pain ≥3 months, and CSRS was determined using the central sensitization inventory. About 69.23% of the sample had CMP (76.85% of females and 56.56% of males). About 60% of people with CMP showed a high level of CSRS severity (66.67% females and 44.93% males). Females presented significantly higher proportions of CMP (p < .001), and there was an association between CSRS severity and being female (p = .004). Chilean victims of PV during the 1973 to 1990 dictatorship presented a high prevalence of CMP and high-level CSRS severity. Both conditions affected females more than males. Future studies are needed to further delve into these variables' behavior and their influence on the quality of life in this population.

Activation of NOS-cGMP pathways promotes stress-induced sensitization of behavioral responses in zebrafish.

Nitric oxide (NO) is a molecule involved in plasticity across levels and systems. The role of NOergic pathways in stress-induced sensitization (SIS) of behavioral responses, in which a particular stressor triggers a state of hyper-responsiveness to other stressors after an incubation period, was assessed in adult zebrafish. In this model, adult zebrafish acutely exposed to a fear-inducing conspecific alarm substance (CAS) and left undisturbed for an incubation period show increased anxiety-like behavior 24 h after exposure. CAS increased forebrain glutamate immediately after stress and 30 min after stress, an effect that was accompanied by increased nitrite levels immediately after stress, 30 min after stress, 90 min after stress, and 24 h after stress. CAS also increased nitrite levels in the head kidney, where cortisol is produced in zebrafish. CAS-elicited nitrite responses in the forebrain 90 min (but not 30 min) after stress were prevented by a NOS-2 blocker. Blocking NOS-1 30 min after stress prevents SIS; blocking NOS-2 90 min after stress also prevents stress-induced sensitization, as does blocking calcium-activated potassium channels in this latter time window. Stress-induced sensitization is also prevented by blocking guanylate cyclase activation in both time windows, and cGMP-dependent channel activation in the second time window. These results suggest that different NO-related pathways converge at different time windows of the incubation period to induce stress-induced sensitization.

Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives.

OBJECTIVE: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. METHODS: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. RESULTS: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. CONCLUSION: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.

A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain.

Neuropathic pain arises from injuries to the nervous system in diseases such as diabetes, infections, toxicity, and traumas. The underlying mechanism of neuropathic pain involves peripheral and central pathological modifications. Peripheral mechanisms entail nerve damage, leading to neuronal hypersensitivity and ectopic action potentials. Central sensitization involves a neuropathological process with increased responsiveness of the nociceptive neurons in the central nervous system (CNS) to their normal or subthreshold input due to persistent stimuli, leading to sustained electrical discharge, synaptic plasticity, and aberrant processing in the CNS. Current treatments, both pharmacological and non-pharmacological, aim to alleviate symptoms but often face challenges due to the complexity of neuropathic pain. Neuromodulation is emerging as an important therapeutic approach for the treatment of neuropathic pain in patients unresponsive to common therapies, by promoting the normalization of neuronal and/or glial activity and by targeting cerebral cortical regions, spinal cord, dorsal root ganglia, and nerve endings. Having a better understanding of the efficacy, adverse events and applicability of neuromodulation through pre-clinical studies is of great importance. Unveiling the mechanisms and characteristics of neuromodulation to manage neuropathic pain is essential to understand how to use it. In the present article, we review the current understanding supporting dorsal root ganglia and spinal cord neuromodulation as a therapeutic approach for neuropathic pain.

Evaluation of multitarget drugs on the expression of cocaine-induced locomotor sensitization in male rats: A comparative study.

Purpose: - Cocaine use disorder (CUD) is a complex disease. Several studies have shown the efficacy of multitarget drugs used to treat CUD. Here we compare the efficacy of mirtazapine (MIR), pindolol (PIN), fluoxetine (FLX), risperidone (RIS), trazodone (TRZ), ziprasidone (ZPR), ondansetron (OND), yohimbine (YOH), or prazosin (PRZ), to reduce long-term cocaine-induced locomotor activity and the expression of cocaine-induced locomotor sensitization in rats. Methods: - The study consists of four experiments, which were divided into four experimental phases. Induction (10 days), cocaine withdrawal (30 days), expression (10 days), and post-expression phase (10 days). Male Wistar rats were daily dosed with cocaine (10 mg/kg; i.p.) during the induction and post-expression phases. During drug withdrawal, the MIR, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ were administered 30 min before saline. In the expression, the multitarget drugs were administered 30 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min.During the agonism phase, in experiment four, 8-OH-DPAT, DOI, CP-809-101, SR-57227A, or clonidine (CLO) was administered 30 min before MIR and 60 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min. Results: -MIR, FLX, RIS, ZPR, OND, or PRZ attenuated the cocaine-induced locomotor activity and cocaine locomotor sensitization. PIN, TRZ, and YOH failed to decrease cocaine locomotor sensitization. At the optimal doses used, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ failed to attenuate long-term cocaine locomotor activation. MIR generated a decrease in cocaine-induced locomotor activity of greater magnitude and duration than the other multitarget drugs evaluated. Conclusion: - At the optimal doses of multitarget drugs evaluated, MIR was the multitarget drug that showed the greatest long-term cocaine-induced behavior effects compared to other multitarget drugs.

Prenatal and postnatal cocaine exposure enhances the anxiety- and depression-like behaviors in rats during cocaine withdrawal.

Prenatal drug exposure is a public health problem, which results in profound behavioral problems during childhood and adolescence, mainly represented by an increase in the risk of cocaine abuse at an early age. In rodents, prenatal and postnatal cocaine exposure enhanced locomotor activity and cocaine- or nicotine-induced locomotor sensitization. Various authors consider that the adverse emotional states (anxiety and depression) that occur during cocaine withdrawal are the main factors that precipitate, relapse, and increase chronic cocaine abuse, which could increase the risk of relapse of cocaine abuse. Therefore, the objective of this study was to characterize anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal in rats born to females exposed prenatally and postnatally to cocaine. A group of pregnant female Wistar rats were administered daily from day GD0 to GD21 with cocaine (cocaine preexposure group), and another group of pregnant female rats was administered daily with saline (saline preexposure group). Of the litters resulting from the cocaine-pre-exposed and saline-pre-exposed pregnant female groups, only the male rats were used for the recording of the anxiety- and depression-like behaviors at different times (30, 60, 90, and 120 days) of cocaine withdrawal The study found that prenatal and postnatal cocaine exposure dose-dependent enhanced anxiety- and depression-like behaviors. This suggests that prenatal and postnatal cocaine exposure can result in enhanced vulnerability to cocaine abuse in young and adult humans.

Characterization and applicability of a novel physiologically relevant 3D-tetraculture bronchial model for in vitro assessment of respiratory sensitization.

Chemical Respiratory Allergy (CRA) is triggered after exposure to Low Molecular Weight (LMW) sensitizers and manifests clinically as asthma and rhinitis. From a risk/toxicity assessment point of view, there are few methods, none of them validated, for evaluating the respiratory sensitization potential of chemicals once the in vivo-based models usually employed for inhalation toxicity addressment do not comprise allergenicity endpoints specifically. Based on that, we developed, characterized, and evaluated the applicability of a 3D-tetraculture airway model reconstructed with bronchial epithelial, fibroblasts, endothelial and monocytic cell lines. Moreover, we exposed the tissue to maleic anhydride (MA) aerosols to challenge the model and subsequently assessed inflammatory and functional aspects of the tissue. The reconstructed tissue presented phenotypic biomarkers compatible with human bronchial epithelium, and MA aerosol exposure triggered an increased IL-8 and IL-6 production, reactive oxygen species (ROS) formation, and apoptosis of epithelial cells. Besides, augmented IL-8 production by monocytic cells was also found, correlating with dendritic cell activation within the co-culture model after MA exposure. Our results demonstrated that the 3D-tetraculture bronchial model presents hallmarks related to human airways' structure and function. Additionally, exposure to a respiratory sensitizer induced inflammatory and functional alterations in the reconstructed tissue, rendering it a valuable tool for exploring the mechanistic framework of chemically induced respiratory sensitization.

Pain Patterns of the Temporomandibular Joint Dysfunction and Implications of Stress-Related Behaviors: A Pilot Study / Patrones de Dolor de la Disfunción de la Articulación Temporomandibular e Implicaciones de los Comportamientos Relacionados con el Estrés: Un Estudio Piloto

SUMMARY: Temporomandibular joint dysfunction interferes with the quality of life and activities of daily living among patients. The symptoms of temporomandibular dysfunction, including pain and clicking and popping sounds, are worsened during stressful events, and patients report increased pain around the temporomandibular joint. Stress-related behaviors, such as teeth clenching and teeth grinding, are commonly reported as increasing during stress. The prevalence of temporomandibular dysfunction and stress-related behaviors is reported differently in the literature. Stress in higher education is common. The purpose of this pilot study was to investigate the prevalence of temporomandibular joint dysfunction and stress-related behaviors among staff members at a local University. The study also sought to explore pain patterns described by people experiencing temporomandibular joint dysfunction and the relationship between stress-related behaviors and pain symptoms experienced. Further, the impact of stress on symptoms experienced by people with temporomandibular dysfunction was investigated in this pilot study.

La disfunción de la articulación temporomandibular interfiere con la calidad de vida y las actividades de la vida diaria entre los pacientes. Los síntomas de la disfunción temporomandibular, incluidos el dolor y los chasquidos, empeoran durante los eventos estresantes, y los pacientes informan un aumento del dolor alrededor de la articulación temporomandibular. Los comportamientos relacionados con el estrés, como apretar y rechinar los dientes, suelen aumentar durante el estrés. La prevalencia de la disfunción temporomandibular y los comportamientos relacionados con el estrés se informa de manera diferente en la literatura. El estrés en la educación superior es común. El propósito de este estudio piloto fue investigar la prevalencia de la disfunción de la articulación temporomandibular y los comportamientos relacionados con el estrés entre los miembros del personal de una universidad local. El objetivo del estudio además fue explorar los patrones de dolor descritos por personas que experimentan disfunción de la articulación temporomandibular y la relación entre los comportamientos relacionados con el estrés y los síntomas de dolor experimentados. Además, en este estudio piloto se investigó el impacto del estrés en los síntomas que experimentan las personas con disfunción temporomandibular.

Tropical high altitude and severe asthma in adults: house dust mite sensitization and phenotypic distribution.

BACKGROUND: There is a lack of information on house dust mite (HDM) sensitization and phenotype distribution in patients with severe asthma (SA) living permanently at high-altitude (HA) in tropical regions, which may be different. OBJECTIVE: The aim of this study was to characterize adults with SA in a tropical high altitude city (2,640 m): Bogotá, Colombia. MATERIAL AND METHODS: This observational cross-sectional study included severe asthmatic outpatients (n = 129) referred to the ASMAIRE program of the Fundación Neumológica Colombiana in Bogotá (2,640 m). Clinical history, spirometry, total IgE, blood eosinophils, and skin prick test (SPT), including HDM allergens, were performed. Phenotype definitions: Allergic/atopic (AA): IgE ≥100 IU/mL and/or at least one positive SPT; eosinophilic (EOS): blood eosinophils ≥300 cells/µL; type 2-high: AA and/or EOS phenotype; type 2-low: non-AA/non-EOS phenotype (IgE <100 IU/mL, negative SPT, and blood eosinophils <300 cells/µL). RESULTS: A total of 129 adults with SA were included, 79.8% female. Phenotype distribution: AA: 61.2%; EOS: 37.2%; type 2-high: 72.1%; type 2-low: 27.9%. Among AA patients, HDM sensitization was present in 87% and 34.9% were non-eosinophilic. There was a significant overlap between the phenotypes. CONCLUSIONS: In contrast to non-tropical high-altitude regions, we found a high frequency of HDM sensitization in patients with AA phenotype living in a tropical high-altitude city. We also found a discrete lower frequency of EOS phenotype with no other significant differences in the phenotypic distribution compared to that described at low altitudes. We propose that tropical location may modify the effect of high altitude on HDM concentrations and allergenicity.

Clinical features of chronic primary pain in individuals presenting painful temporomandibular disorder and comorbidities.

BACKGROUND: The diagnosis of chronic primary pain (CPP), according to the recently released International Classification of Disease (ICD-11) criteria, refers to conditions with complex aetiologies. CPP is characterized by specific clinical features such as generalized sensory hypersensitivity and widespread pain, and is associated with functional disability and emotional distress. OBJECTIVE: This study investigated clinical features of CPP in individuals with painful temporomandibular disorders (TMD) and comorbidities (fibromyalgia, migraine and/or tension-type headache). METHODS: This cross-sectional study was conducted with a sample of 129 individuals. Painful TMD, fibromyalgia and primary headaches were evaluated based on well-established international criteria. Generalized sensory hypersensitivity was assessed using psychophysical tests. Symptoms of anxiety and depression were assessed by the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9. The Central Sensitization Inventory was applied to assess central sensitization-related symptoms and the Pittsburg Sleep Quality Index to evaluate the quality of sleep. The presence of widespread pain was assessed using a body map. The sample was stratified into three groups: control (n = 25), TMD-painful TMD only (n = 35) and TMD + Cm-painful TMD and comorbidities (n = 69). Statistical analysis was performed using one-way ANOVA, chi-squared test and ANCOVA, considering gender as a covariate (α = .05). RESULTS: Compared to controls, individuals presenting painful TMD and comorbidities showed lower pressure pain thresholds in all evaluated areas (p ≤ .012) and a higher number of painful areas in the body (p = .001). They presented more symptoms of anxiety (p = .040) and depression (p = .018), and a higher score in the Central Sensitization Inventory (p ≤ .006) than the other groups. CONCLUSION: Individuals with painful TMD and comorbidities presented more clinical features of CPP compared to those affected by TMD only.

Aeroallergen sensitization patterns among patients with chronic rhinitis with or without concomitant asthma.

OBJECTIVES: The aim of this study was to explore the differences in the pattern of allergen sensitization in CR individuals without or with asthma, according to asthma severity. METHODS: A total of 1066 adults were evaluated. Asthma and chronic/allergic rhinits were identified by specialists, questionnaries and skin-prick test. The phenotypic characterization was avaliable from skin-prick test to an aeroallergen extended panel, total IgE and pulmonary function. Using questionnaires and clinical evaluation, participants were classified into the groups: chronic rhinitis alone (CRA) and chronic rhinitis + asthma, the latter subdivided into CR + mild asthma (CRMA) and CR + moderate to severe asthma (CRMSA). Aerollergen sensitization was defined by a positive prick test to one or more allergens associated with nasal symptoms and/or asthma. The association between CR and asthma was evaluated by multivariable logistic regression. The evidence of effect modification of pattern of sensitization in CR on the association with asthma severity and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. RESULTS: Frequency of sensitization to aeroallergens was higher in association with asthma in comparison to CRA (CRMA 70.4%; CRMSA 65.0%; CRA 47.0%; p = 0.000). Similarly, the presence of asthma was associated to aeroallergen multiple sensitization (51.5%) (OR = 2.10, 95% CI 1.27-3.50). Additionally, the sensitization to mites, cockroaches, animal epithelium, grasses, and molds, were higher in asthma (56.8%, 24.3%, 12%, 7.13% and 10.3%, respectively). Sensitization to Alternaria alternata, Cladosporium herbarum and dog epithelium was exclusive in asthma groups. A concomitant asthma diagnosis was directly associated with a positive allergen sensitization at least one allergen (62.7%, OR = 2.45, 95% CI 1.80-3.34) and polissensitization (51.5%, OR = 2.10, 95% CI 1.27-3.50). CONCLUSION: Asthma is associated with multiple allergen sensitization among patients with CR. Some unique profiles of aeroallergen sensitization were observed in patients with CR and asthma. Nevertheless, no difference was found in the sensitization in relation to asthma severity, which suggest atopy is not the main underlying mechanism for asthma severity among patients with CR. LEVEL OF EVIDENCE: Level 3.

Study on the antidepressant activity of (2R,6R; 2S,6S)-Hydroxynorketamine (HNK) and its derivatives

Abstract Objective: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. Methods: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. Results: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. Conclusion: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.

On the mechanism of visible-light sensitized photosulfoxidation of toluidine blue O.

We report on the formation of toluidine blue O (TBO) sulfoxide by a self-sensitized photooxidation of TBO. Here, the photosulfoxidation process was studied by mass spectrometry (MS) and discussed in the context of photodemethylation processes which both contribute to TBO consumption over time. Analysis of solvent effects with D2O, H2O, and CH3CN along with product yields and MS fragmentation patterns provided mechanistic insight into TBO sulfoxide's formation. The formation of TBO sulfoxide is minor and detectable up to 12% after irradiation of 3 h. The photosulfoxidation process is dependent on oxygen wherein instead of a type II (singlet oxygen, 1O2) reaction, a type I reaction involving TBO to reach the TBO sulfoxide is consistent with the results. Density functional theory results point to the formation of the TBO sulfoxide by the oxidation of TBO via transiently formed peroxyl radical or thiadioxirane intermediates. We discover that the TBO photosulfoxidation arises competitively with TBO photodemethylation with the latter leading to formaldehyde formation.