Real-World Evidence of Antipsychotic Monotherapy Versus Polypharmacy in the Treatment of Schizophrenia Spectrum Disorders.

PURPOSE/BACKGROUND: It is still not well known whether antipsychotic monotherapy versus polypharmacy differs in terms of efficacy in the emergency department (ED) utilization, presentation with agitation/aggression, and rehospitalization in schizophrenia spectrum disorders (SSD) patients. This study aimed to determine the effectiveness of antipsychotic monotherapy and polypharmacy for these outcomes in the real world. METHODS/PROCEDURES: The study was conducted with electronic health records of 669 SSD patients admitted to the ED. Patients were evaluated in 4 groups according to antipsychotic use at the first admission to ED: antipsychotic noncompliance for more than 90 days, antipsychotic noncompliance for 15 to 90 days, antipsychotic monotherapy, and polypharmacy. All patients followed up for at least 1 year after index admission. The primary outcomes determined an association between antipsychotic monotherapy versus polypharmacy and all-cause psychiatric hospitalization between the groups after index admission in the SSD. FINDINGS/RESULTS: The groups, including patients with antipsychotic noncompliance, had higher ED visits, more hospitalizations, and more admissions with agitation/aggression compared with antipsychotic monotherapy or polypharmacy. However, no differences were found between monotherapy and polypharmacy groups regarding these outcomes. In addition, there was no difference in the risk of hospitalization in monotherapy antipsychotic users compared with polypharmacy users. Patients discharged with monotherapy or polypharmacy also had similar rehospitalization rates at follow-up. IMPLICATIONS/CONCLUSIONS: There is no positive evidence that recommending polypharmacy over antipsychotic monotherapy is superior with regard to the resulting frequency of ED visits, ED admissions with agitation/aggression, hospitalization, and rehospitalization. In this context, antipsychotic monotherapy may be preferred over polypharmacy in patients who are not resistant to treatment.

An In Vitro Study for the Role of Schizophrenia-Related Potential miRNAs in the Regulation of COMT Gene.

This study aimed to analyze the possible association of miR-30a-5p, miR-30e-5p, and miR-34a-5p identified as potential candidate miRNAs in schizophrenia, with the COMT gene. Candidate miRNAs were obtained from the TargetScan database. The SH-SY5Y human neuroblastoma cell line was used as a cellular model for schizophrenia. miR-30a-5p, miR-30e-5p, and miR-34a-5p mimics were transfected into the SH-SY5Y cell line. Total RNA was isolated from transfected cells and RNA-IP samples and reverse transcripted for miRNA and mRNA analysis. RT-qPCR and western blot were performed to observe changes in expression levels of COMT. RNA-immunoprecipitation was performed to determine RNA-protein interactions after mimic transfection. In the study, it was observed that COMT gene expression levels decreased significantly after miR-30a-5p and miR-34a-5p expressions, whereas increased significantly as a result of miR-30e-5p transfection. RNA-IP data have shown that the amount of COMT pulled down by Ago2 was increased after miR-30a-5p and miR-34a-5p transfections. RNA-IP results revealed that miR-30a-5p and miR-34a-5p are direct targets for the COMT gene.

Determination of copper and cobalt in different tea samples at trace levels by FAAS after preconcentration with a novel iron PAMAM-OH-encapsulated magnetic nanoparticle as SPE sorbent.

Environmental contamination caused by heavy metals is a significant global concern. The presented study investigated the efficiency of iron PAMAM-OH encapsulated magnetic nanoparticles (Fe-MNP-G2-OH) as sorbent for the preconcentration of copper and cobalt from tea samples. High metal-chelating ethylenediamine core polyamidoethanol generation-2 (PAMAM-G2-OH) was encapsulated with iron oxide (Fe3O4) to synthesize the sorbent. Limit of detection (LOD) values for copper and cobalt extracted and detected by the developed Fe-MNP-G2-OH -SPE-FAAS method were 0.52 and 1.1 µg L-1, respectively. There were 230- and 101-fold improvement in detection limits for copper and cobalt, respectively, when compared to direct FAAS measurement. The percent recovery results for the analytes in green and black tea samples ranged from 93 to 107%, with low relative standard deviation (%RSD) values. The synthesis of nanoparticle was carried out through a unique method, which was characterized by thermogravimetric analysis (TGA), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR) methods. The analytical results demonstrated the applicability and effectiveness of Fe-MNP-G2-OH nanoparticles on the preconcentration of copper and cobalt from tea samples and the developed method is suitable for the trace detection of heavy metals by FAAS method. To the best our knowledge, this is the first study where copper and cobalt in green and black tea samples were extracted by Fe-MNP-G2-OH adsorbent and precipitation of the adsorbent during its synthesis was carried out in acetone medium rather than aqueous one.

Inflammatory markers in exhaled breath condensate in nonasthmatic children with food allergy.

Allergy is a systemic inflammation; therefore, although the allergic symptom may be seen in a specific organ system, the effects of this inflammation may be seen in other organs. interleukin (IL) IL4, IL5 and IL13 are the major Th2 cytokines and e-cadherin is an epithelial barrier protein. The objective of this research was to assess indicators of inflammation specific to Th2 responses and proteins related to the protective barrier of the airway's inner lining. These assessments were conducted using exhaled breath condensate (EBC), which provides insights into peripheral airway conditions of children suffering from food allergies. The study had 24 patients with food allergy and 24 control individuals younger than three years of age with no history of food reaction. The diagnosis of food allergy was based on food allergen-specific IgE and skin prick test positivity in our clinic and oral food testing in selected cases. EBC samples were obtained by Ecoscreen (Jaegar, Hoechberg, Germany). IL4, IL5, IL13 and E-cadherin levels were measured in these samples by enzyme linked immunoassay. The group of children with food allergies, consisting mainly of 14 girls, had a median age of 16 months, whereas the control group, which included 11 girls, had a median age of 15 months (p= 0.89). Comparing the two groups, children with food allergies exhibited notably lower levels of IL-13 in the EBC compared to the control group (median values of 59.14 and 76.36, respectively,p= 0.02). Conversely, the concentration of IL-4 in the EBC was significantly higher in children with food allergies (median values of 1.94 and 1.29, respectively,p= 0.003). However, the levels of IL-5 and e-cadherin showed no significant differences between the two groups (withp-values of 0.74 and 0.09, respectively) as shown in table1. High level of IL-4 despite the low level of IL-13 in the EBC of children having food allergy may be indicative of an early inflammatory phase that is not yet in the effector phase. Studies about the evolution of this process later in life are needed to assess the role of airway inflammation in children with food allergy who develop asthma.

Research Publications from the ATS MECOR Program in Turkiye.

Background: The American Thoracic Society (ATS) Methods in Epidemiologic, Clinical, and Operations Research (MECOR) Program aims to build research capacity in low and middle-income countries. MECOR has three levels, during which students learn to develop a research protocol and write a manuscript. MECOR Turkiye has been offered every year since 2008. Objective: The aim of this paper is to report the number and impact of published articles generated from research questions developed by students in levels 1, 2, and 3 of the ATS MECOR Program in Turkiye between 2008 and 2018. Methods: We collected the research questions developed in all levels of the ATS MECOR Program in Turkiye between 2008 and 2018. We searched Google Scholar, PubMed, Web of Science, and ResearchGate in April 2022 to see how many of these research questions were published as articles and, if published, in which journals. Results: Of the 176 research questions collected, 49 had been developed in level 1, 82 had been developed in level 2, and 45 had been developed in level 3. Of those 176 research questions, 55 (31.3%) generated articles that were accepted for publication. The frequency of published articles based on MECOR-developed research questions increased linearly as the course level in which they were developed increased (18.4% in level 1, 30% in level 2, 46.7% in level 3; P = 0.012; linear-by-linear association, P = 0.003). The median time from the development of the research question to publication was three years overall and did not differ significantly among the course levels (P = 0.36). Of the research questions developed, 43 were published in Science Citation Index or Science Citation Index Expanded-indexed journals. Conclusion: Acceptance of an article for publication is one way to measure the impact of the ATS MECOR Program. Our data describe significant research output among our participants, which increases with their length of participation in the program.

Adulthood asthma as a consequence of childhood adversity: a systematic review of epigenetically affected genes.

There is an accumulating data that shows relation between childhood adversity and vulnerability to chronic diseases as well as epigenetic influences that in turn give rise to these diseases. Asthma is one of the chronic diseases that is influenced from genetic regulation of the inflammatory biomolecules and therefore the hypothesis in this research was childhood adversity might have caused epigenetic differentiation in the asthma-related genes in the population who had childhood trauma. To test this hypothesis, the literature was systematically reviewed to extract epigenetically modified gene data of the adults who had childhood adversity, and affected genes were further evaluated for their association with asthma. PRISMA guidelines were adopted and PubMed and Google Scholar were included in the searched databases, to evaluate epigenetic modifications in asthma-related genes of physically, emotionally or sexually abused children. After retrieving a total of 5245 articles, 36 of them were included in the study. Several genes and pathways that may contribute to pathogenesis of asthma development, increased inflammation, or response to asthma treatment were found epigenetically affected by childhood traumas. Childhood adversity, causing epigenetic changes in DNA, may lead to asthma development or influence the course of the disease and therefore should be taken into account for the prolonged health consequences.

May the first-line treatment for foreign body aspiration in childhood be flexible bronchoscopy?

INTRODUCTION: Rigid bronchoscopy (RB) is the traditional treatment in foreign body (FB) aspiration in childhood but is a traumatic and invasive procedure. However, flexible optic bronchoscopy (FoB) is a noninvasive and nontraumatic respiratory intervention. The aim of this study was to evaluate FoB as a first-line treatment modality in pediatric cases presenting with a preliminary diagnosis of FB aspiration. METHODS: Subjects who underwent FoB under general anesthesia with the preliminary diagnosis of FB aspiration were enrolled in this cross-sectional study. Two cases were inherited from pediatric surgery because they were not removed with FoB. The demographic, clinical, and radiological findings at the presentation were recorded. Results of success rate and complications were recorded. RESULTS: Among the FB aspiration cases age range of 7 months to 16 years. FoB demonstrated a FB in the airways of 31 (62.2%) subjects. The duration of the symptoms in the subjects was 9.1 ± 8.8 days. Three of the cases were taken over from pediatric surgery because they were not removed with RB. Most commonly encountered FB's were organic materials (n = 20, 64%). FoB was successful in removing the FB from the proximal and also distal airways in 93% of the subjects. No significant complications and side effects were observed except post-FoB cough. CONCLUSION: This result has shown that FoB for the treatment of FB aspiration is successful in removing FB aspiration from both the proximal and distal airway that the RB cannot remove. Furthermore, FoB did not have any significant airway complication. FoB may be used as the first-line treatment modality for FB aspiration instead of RB in childhood the fact that noninvasive and nontraumatic respiratory intervention.

E-Cadherin: An Important Functional Molecule at Respiratory Barrier Between Defence and Dysfunction.

While breathing, many microorganisms, harmful environmental particles, allergens, and environmental pollutants enter the human airways. The human respiratory tract is lined with epithelial cells that act as a functional barrier to these harmful factors and provide homeostasis between external and internal environment. Intercellular epithelial junctional proteins play a role in the formation of the barrier. E-cadherin is a calcium-dependent adhesion molecule and one of the most important molecules involved in intercellular epithelial barier formation. E-cadherin is not only physical barrier element but also regulates cell proliferation, differentiation and the immune response to environmental noxious agents through various transcription factors. In this study, we aimed to review the role of E-cadherin in the formation of airway epithelial barier, its status as a result of exposure to various environmental triggers, and respiratory diseases associated with its dysfunction. Moreover, the situations in which its abnormal activation can be noxious would be discussed.

Diversity of developing peripheral glia revealed by single-cell RNA sequencing.

The peripheral nervous system responds to a wide variety of sensory stimuli, a process that requires great neuronal diversity. These diverse neurons are closely associated with glial cells originating from the neural crest. However, the molecular nature and diversity among peripheral glia are not understood. Here, we used single-cell RNA sequencing to profile developing and mature glia from somatosensory dorsal root ganglia and auditory spiral ganglia. We found that glial precursors (GPs) in these two systems differ in their transcriptional profiles. Despite their unique features, somatosensory and auditory GPs undergo convergent differentiation to generate molecularly uniform myelinating and non-myelinating Schwann cells. By contrast, somatosensory and auditory satellite glial cells retain system-specific features. Lastly, we identified a glial signature gene set, providing new insights into commonalities among glia across the nervous system. This survey of gene expression in peripheral glia constitutes a resource for understanding functions of glia across different sensory modalities.

Geographical barriers to timely diagnosis of cystic fibrosis and anxiety level of parents during newborn screening in Turkey.

BACKGROUND: Despite the availability of cystic fibrosis (CF) screening countrywide, diagnostic delay is still a crucial issue. The objectives of this study were to explore the stages of the NBS process, determine the risk factors associated with diagnostic delay and evaluate parent anxiety and experience throughout the process. METHODS: This is a multicenter cross-sectional study. A questionnaire was completed by parents of newborns diagnosed with CF via NBS in 17 centers. Socio-demographic characteristics, parent knowledge and experiences related to NBS, sweat test availability in the region of residence, and time to the definitive CF diagnosis were assessed through this questionnaire. Parents' anxiety levels were evaluated through the State-Trait Anxiety Inventory scales 1 and 2. Delayed diagnosis (DD) was defined as a definite CF diagnosis beyond the 8th week of life. Predictors of delayed CF diagnosis were evaluated by univariate and multivariate analysis. RESULTS: A total of 220 CF patients diagnosed via NBS were enrolled; 82 (37.3%) babies had DD. Multivariable analysis indicated that residence in the Southeast Anatolia region of Turkey (OR = 10.79, 95% CI = 2.37-49.2) was associated with a higher incidence of DD compared with other regions in Turkey. Of the total, 216 (98.1%) of the caregivers regarded the NBS program as useful and 180 (82%) reported high anxiety levels. CONCLUSION: The organization of newborn screening should take into account regional and socio-cultural characteristics to improve the early diagnosis of CF and also reduce the anxiety level of parents.

Sentinel serosurveillance of backyard hens proved West Nile virus circulation in the western provinces of Turkey.

West Nile virus (WNV) is a mosquito-borne virus of a re-emergence importance with a wide range of vertebrate hosts. Granted, it causes asymptomatic infection, but fatal cases and neurologic disorders were also recorded, especially in humans, horses and some exposed birds. The virus is globally spread and birds are considered an amplifying and reservoir host of WNV, helping to spread the disease due to their close contact with main hosts. In this study, we aimed to detect the presence of antibodies against WNV in backyard hens that were reared in the western Anatolian part of Turkey. A total of 480 chicken sera were randomly collected from six provinces in the west of Turkey (Mugla, Izmir, Aydin, Afyonkarahisar, Kutahya and Manisa) with 80 samples from each province (40 in spring and 40 in fall seasons). They were tested by using a competitive ELISA method to identify the specific avian antibodies of IgG that produced against the WNV envelope proteins (pr-E). Twelve of 480 (2.5%) sera were found seropositive, three of these positive sera were detected from the Izmir province (3.75%) collected in the spring session and the other nine positive sera were detected from the Mugla province (11.25%) collected in the fall session. Both of these provinces are located seaside and have suitable climate conditions for vectors of infection. The results indicated that WNV infection is in circulation in these provinces, and that may put the other susceptible vertebrates under risk of infection.

Quantification of palladium in wastewater samples by matrix-matching calibration strategy assisted deep eutectic solvent based microextraction.

An efficient, sensitive, and easy deep eutectic solvent based (DESb) liquid phase microextraction (LPME) method was developed to preconcentrate palladium for quantification at trace level by a flame atomic absorption spectrometry (FAAS) system, equipped with a lab made slotted quartz tube (SQT). All parameters of the DESb-LPME-SQT-FAAS system were optimized to lower the detection limit of the system. Using the optimized conditions, quantification and detection limits were obtained as 24.7 and 7.4 µg L-1, respectively, which are compatible with the literature findings. Detection power of the FAAS system was enhanced by almost 50-fold using the optimum method based on LOD comparison. Recovery experiments were also performed with spiked wastewater matrix to examine the applicability/validity of the proposed method. The % recovery results were calculated between 85 and 91%. This established that the applicability of the developed method is high, and determination of this element in complex matrix can be performed accurately using the developed method.

Two different methods of lidocaine inhalation before diagnostic flexible bronchoscopy: effects on post-bronchoscopy respiratory symptoms

Background/aim: Use of topical anesthesia before flexible bronchoscopy for the evaluation of the upper airways prevents cough and stridor during and after the procedure while reducing the need for sedation. In practice, lidocaine is the medication of choice before bronchoscopy. There various types of nebulizers used for inhalation treatments. In this study, we compared the respiratory tract symptoms after flexible bronchoscopy between children who received pre-procedure topical lidocaine with mesh or jet nebulizers. Materials and methods: We enrolled 4­18 years old subjects that underwent flexible bronchoscopy due to treatment-resistant asthma in this retrospective case-control study. Twenty subjects received topical lidocaine with jet nebulizers while 20 received it with mesh nebulizers. Age, sex, duration of bronchoscopy, duration of anesthesia, time to awaken, and time to recovery were recorded as well as cough and laryngospasm scores after flexible bronchoscopy. Results: Severe cough after flexible bronchoscopy was not encountered in the mesh nebulizers group but was seen in 10% of the jet nebulizers group (p = 0.027). On the other hand, age, sex, duration of bronchoscopy, duration of anesthesia, time to awaken, and time to recovery were not significantly different between the mesh and jet nebulizer groups (p = 0.44, 0.34, 0.51, 0.88, 0.88, and 0.22, respectively). Moreover, croup and laryngospasm scores between the two groups were similar (p = 0.62, 0.50 respectively). Cough score was significantly worse jet nebulizers group (p = 0.03). Conclusion: Topical lidocaine application with mesh nebulizers decreases the most common complication, cough, after flexible bronchoscopy in children more effectively compare to jet nebulizers. Thus, mesh nebulizers may be a faster way of nebulization before flexible bronchoscopy as an alternative to jet nebulizers.

Anti-VEGF treatment suppresses remodeling factors and restores epithelial barrier function through the E-cadherin/ß-catenin signaling axis in experimental asthma models.

Besides maintaining a physical barrier with adherens junctional (AJ) and tight junctional proteins, airway epithelial cells have important roles in modulating the inflammatory processes of allergic asthma. E-cadherin and ß-catenin are the key AJ proteins that are involved in airway remodeling. Various mediators such as transforming growth factor-ß (TGF-ß), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), tumor necrosis factor-α (TNF-α) and angiogenic factors, such as vascular endothelial growth factor (VEGF), are released by the airway epithelium in allergic asthma. The signaling pathways activated by these growth factors trigger epithelial-mesenchymal transition (EMT), which contributes to fibrosis and subsequent downregulation of E-cadherin. The present study used a mouse asthma model to investigate the effects of anti-VEGF, anti-TNF and corticosteroid therapies on growth factor and E-cadherin/ß-catenin expression. The study used 38 male BALB/c mice, divided into 5 groups. A chronic mouse asthma model was created by treating 4 of the groups with inhaled and intraperitoneal ovalbumin (n= 8 per group). Saline, anti-TNF-α (etanercept), anti-VEGF (bevacizumab) or a corticosteroid (dexamethasone) were applied to each group by intraperitoneal injection. No medication was administered to the control group (n=6). Immunohistochemistry for E-cadherin, ß-catenin and growth factors was performed on lung tissues and protein expression levels assessed using H-scores. Statistically significant differences were observed in E-cadherin, ß-catenin, EGF, FG, and PFGF (P<0.001 for all) as well as the IGF H-scores between the five groups (P<0.005). Only anti-VEGF treatment caused E-cadherin and ß-catenin levels to increase to the level of non-asthmatic control groups (P>0.005). All treatment groups had reduced TGF-ß, PDGF and FGF H-scores in comparison with the untreated asthma group (P=0.001). The EGF and IGF levels were not significantly different between the untreated asthmatic and non-asthmatic controls. The results suggested that anti-VEGF and TNF-α inhibition treatments are effective in decreasing growth factors, in a similar manner to conventional corticosteroid treatments. Anti-VEGF and TNF inhibition therapy may be an effective treatment for remodeling in asthma while offering an alternative therapeutic option to steroid protective agents. The data suggested that anti-VEGF treatment offered greater restoration of the epithelial barrier than both anti-TNF-α and corticosteroid treatment.

European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16†years.

BACKGROUND: Diagnosing asthma in children represents an important clinical challenge. There is no single gold-standard test to confirm the diagnosis. Consequently, over- and under-diagnosis of asthma is frequent in children. METHODS: A task force supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years using nine Population, Intervention, Comparator and Outcome (PICO) questions. The task force conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full-text articles. All task force members approved the final decision for inclusion of research papers. The task force assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The task force then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The task force formulated recommendations using the GRADE Evidence to Decision framework. CONCLUSION: Based on the critical appraisal of the evidence and the Evidence to Decision framework, the task force recommends spirometry, bronchodilator reversibility testing and exhaled nitric oxide fraction as first-line diagnostic tests in children under investigation for asthma. The task force recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future.

Maternal psychiatric status and infant wheezing: The role of maternal hormones and cord blood cytokines.

RATIONALE: Maternal psychosocial stress might be associated with development of allergic diseases in the offspring. OBJECTIVES: To evaluate the association of maternal depression and anxiety with ever wheezing and recurrent wheezing among infants and to assess the role of maternal hypothalamo-pituatary-adrenal axis changes and fetal immune response in this association. METHODS: This study encompasses two designs; cohort design was developed to evaluate the association of prenatal depression with development of wheezing in infants while nested case-control design was used to assess the role of maternal cortisol and tetranectin and cord blood interleukin 13 and interferon γ. RESULTS: We enrolled 697 pregnant women. Elementary school graduate mother (odds ratio [OR] = 1.5, p = .06), maternal smoking during pregnancy (OR = 3.4, p = .001), familial history of asthma (OR = 2.7, p < .001) increased the risk of ever wheezing. Elementary school graduate mother (OR = 2.6, p = .002), maternal smoking during pregnancy (OR = 4.8, p < .001) and familial history of asthma (OR = 1.7, p = .01) increased the risk of recurrent wheezing. Maternal previous psychiatric disease, or Edinburgh Postnatal Depression Scale or Spielberger State-Trait Anxiety Inventory scores were not associated with wheezing. Maternal tetranectin levels were significantly higher among never wheezers compared to the ever wheezers (264.3 ± 274.8 vs. 201.6 ± 299.7, p = .04). CONCLUSIONS: In conclusion, the major risk factors for ever wheezing and recurrent wheezing were maternal smoking, level of education and family history of asthma. However, maternal depression and anxiety were not determined as risk factors for wheezing. Maternal tetranectin carries potential as a biomarker for wheezing in the infant.

Fetal Programming: Lung Health and Disease.

Fetal programming is a mechanism whereby stimuli acting on the developing fetus influence the development of the fetus in a way that may set the stage for adult health and disease. These stimuli may be environmental, such as maternal smoking; metabolic, such as the maternal diet and nutrition; or endocrine, such as diabetes or stress, and may extend over several generations. The endocrine system influences fetal programming with effects of insulin, thyroid hormones, and glucocorticoid hormones. Epigenetic information may be modified by DNA methylation, histone modifications, and micro RNAs due to environmental exposures. In this review, we describe the normal development of the lungs and the major factors that may influence lung growth and development with the potential for sequelae into adult life.