Management of Refractory Functional Gastrointestinal Disorders: What Role Should Psychiatrists Have?

Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists' role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, "psyche," "psychiatry," "psychology," "psychiatrist," "psychotropic," and "refractory functional gastrointestinal disorders" (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.

Physical and psychosocial challenges of people with gender dysphoria: a content analysis study.

BACKGROUND: The mismatch between the gender experienced by a person and the gender attributed to him/her leads to gender dysphoria. It seems that people's perception of gender dysphoria is affected by individual, cultural, and sociological factors and these factors affect different aspects of their biological, psychological, and social health. To this end, this qualitative study aimed to identify the physical, psychological, and social challenges of people with gender dysphoria referring to the Department of forensic medicine in Iran. METHODS: This qualitative study was conducted using conventional content analysis on 9 individuals who were selected through purposive sampling. A total of 16 interviews were conducted with 9 participants. Each interview lasted 60-90 min. The participants' gender dysphoria was confirmed by the Department of forensic medicine. The data were collected through face-to-face semi-structured interviews with the participants. RESULTS: The data revealed 3 main categories and 10 subcategories. The main categories were living in agony, confusion, and social concerns. The subcategories were annoying physical characteristics, mental suffering, disturbing sexual changes, concerns about public reaction, helplessness, surrender, the final solution, retreating to isolation, stressful family conditions, and lack of public recognition. CONCLUSION: The findings showed that people with gender dysphoria suffer from some problems including living in agony, confusion, and social concerns. Each of these problems is associated with several challenges. It seems that most of the challenges faced by people with gender dysphoria are caused by unawareness of their conditions by the family and the public, which in turn is caused by the failure of related organizations and experts in this field to provide adequate information about the conditions of these people. Thus, the findings of the present study can have some implications for resolving the challenges faced by people with gender dysphoria.

"Visualization" of pain using cerebral 18F-FDG PET/CT following surgical treatment of lumbar disc herniation.

PURPOSE: We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus. METHODS: Patients scheduled for surgery due to LDH underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography less than two weeks prior to surgery. Their thalamic FDG uptake was measured and expressed as the mean and partial volume corrected mean standardized uptake values (SUVmean and cSUVmean). These measures were compared with patient-related outcome measures collected pre- and 1-year post-operatively: back and leg pain on a 0-100 VAS scale and health-related quality of life as measured by the EuroQol-5D (EQ-5D). RESULTS: Twenty-six patients (ten females) aged 49.7 ± 7.4 (mean ± SD) years were included. There was a significant correlation between painful body side and increased contralateral thalamic uptake of FDG, with regard to cSUVmean values. Correlation analyses including clinical parameters and cSUVmean indicated some association with 1-year change in EQ-5D. CONCLUSION: These preliminary data sustain the hypothesis that unilateral pain in patients with LDH is associated with increased glucose metabolism in the contralateral thalamus, suggesting a central role of thalamus in chronic pain perception.

Anastasis: cell recovery mechanisms and potential role in cancer.

Balanced cell death and survival are among the most important cell development and homeostasis pathways that can play a critical role in the onset or progress of malignancy steps. Anastasis is a natural cell recovery pathway that rescues cells after removing the apoptosis-inducing agent or brink of death. The cells recuperate and recover to an active and stable state. So far, minimal knowledge is available about the molecular mechanisms of anastasis. Still, several involved pathways have been explained: recovery through mitochondrial outer membrane permeabilization, caspase cascade arrest, repairing DNA damage, apoptotic bodies formation, and phosphatidylserine. Anastasis can facilitate the survival of damaged or tumor cells, promote malignancy, and increase drug resistance and metastasis. Here, we noted recently known mechanisms of the anastasis process and underlying molecular mechanisms. Additionally, we summarize the consequences of anastatic mechanisms in the initiation and progress of malignancy, cancer cell metastasis, and drug resistance. Video Abstract.

Selecting the most suitable organizational structure for hospitals: an integrated fuzzy FUCOM-MARCOS method.

BACKGROUND: Previous studies mentioned four organizational structures for hospitals, which are budgetary, autonomous, corporate, and private. Nevertheless, healthcare decision-makers are still required to select the most organizational structure specific to their circumstances. The present study aims to provide a framework to prioritize and select the most suitable organizational structure using multicriteria decision-making (MCDM) methods in Iranian hospitals. METHODS: First, a multicriteria decision-making model consisted of the respective criteria, and alternatives were developed. The pertinent criteria were identified through a systematic literature review. The coefficient weights of the identified criteria were then calculated using FUCOM-F. Finally, organizational structures were prioritized in accordance with the identified criteria using FMARCOS. RESULTS: The findings reveal that income is the most significant criterion in selecting organizational structures for hospitals whereas the number of outpatient visits is the least important. Also, the private structure is the most appropriate, and budgetary style is the least suitable organizational structure for Iranian hospitals. CONCLUSION: Providing a framework in order to select the most appropriate organizational structure could help managers and policymakers of the healthcare sector in Iran and other countries, mainly similar developing countries.

From emotional intelligence to suicidality: a mediation analysis in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a serious mental illness with a high suicidality rate between 40 and 85%. However, little is known concerning psychosocial risk and protective factors associated with suicidal behaviors in this clinical group. The main focus of the present study was on examining the relationship of emotional intelligence (EI) with suicidal behaviors and its mediators (e.g., depression, self-esteem, addiction potential, and disorder severity) among patients with BPD. METHODS: In this cross-sectional study, a total of 220 participants (including 110 patients with BPD and 110 healthy controls) in Zahedan, Iran, were examined using clinical interviewing and self-report measures of EI, suicidal behaviors, depression, self-esteem, addiction potential, and BPD symptom severity. The data were analyzed using SPSS v25.0 software at the significance level of p < 0.05. RESULTS: Our preliminary analysis showed higher levels of EI, depression, and self-esteem in the BPD group in comparison to healthy controls (p < 0.001). Furthermore, our findings showed that higher levels of addiction potential, BPD symptom severity, and depression and lower levels of self-esteem and EI were likely to be related to suicidal behaviors of the BPD group. Our results also supported the overall hypothesis that addiction potential, depression, BPD symptom severity, and self-esteem had a mediating role in the impact of EI on suicidal behaviors in the BPD group. CONCLUSIONS: According to these findings, we have come to believe that training EI possibly plays a directly and/or indirectly potential preventive and therapeutic role in suicidal behaviors among patients with BPD. However, further longitudinal studies must be carried out to clarify the cause and effect relationship between EI, depression, self-esteem, addiction potential, BPD symptom severity, and suicidal behaviors.

Candidate Psychotropics against SARS - CoV - 2: A Narrative Review.

Since few therapeutic options are clinically accessible for coronavirus disease 2019 (COVID-19), effective, safe, and globally available pharmaceuticals need to be urgently developed to prevent severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and alleviate the severity of COVID-19. In this regard, the present paper is intended to provide an extensive review of the clinical and preclinical evidence on the psychotropics' anti-SARS-CoV-2 effects, giving an insight into their potential applications for patients with a proven or high likelihood of COVID-19 pneumonia. The results showed that psychotropic drugs such as melatonin, lithium carbonate, valproate, olanzapine, quetiapine, clozapine, fluoxetine, escitalopram, fluvoxamine, and cannabidiol could help lower the mortality due to SARS-CoV-2 infection. According to these medications' direct immunomodulatory actions against the destructive cytokine storm, as well as other direct/indirect mechanisms (e. g., the endolysosomal pathway modulation, interactions with specific receptors, and membrane fusion), it was perceived that such drugs could effectively weaken the worsened immune response and avoid adult respiratory distress syndrome and acute lung injury. According to the author's analysis of the currently available evidence, there is significant support for psychotropics as complementary interventions during SARS-CoV-2 infection. However, further studies need to be carried out to assess the effects of the above psychotropic drugs in vitro and clinical settings.

A Possible Type IV Hypersensitivity Reaction to Older Antiepileptic Drugs During and After Recovery from COVID-19 Infection.

Nearly two years after the onset of the coronavirus disease 2019 (COVID-19) pandemic, healthcare workers face new and unexpected complications. Although accelerating the vaccination process in recent months has reduced the incidence and mortality of the COVID-19 infection, the general population (particularly vulnerable groups) remains at risk of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Over the last two months, Iran has encountered the fifth wave of the COVID-19 pandemic, i. e., the B.1.617.2 (Delta) variant of the SARS-CoV-2, with faster infectiousness and higher severity and mortality among hospitalized patients 1. Although fever, cough, and expectoration are the most common clinical features of COVID-19, recent studies have indicated an increasing number of skin manifestation reports in the disease. Besides, there is growing evidence that underlying SARS-CoV-2 infection may increase the risk of adverse drug reactions 2. However, the enduring concern in our medical centers in recent days is a raised incidence of Stevens-Johnson syndrome (SJS) in recovered COVID-19 patients following monotherapy with older antiepileptic drugs (0.004 vs. 0.0008% - i. e., 5 times higher than the pre-COVID-19 period) 3. It is worth noting that these patients did not have any history of SJS/toxic epidermal necrolysis (TEN) or additional etiopathogenic factors, including infections, genetic factors (particularly HLA-B*1502 allele), and malignancy. Furthermore, for many years before developing the COVID-19 and recovering from it, they had been treated with the above drugs without showing any cutaneous hypersensitivity reactions. These observational findings raise two important questions: (i) Could a history of the COVID-19 infection be a potential risk factor for type IV hypersensitivity reactions to older antiepileptic drugs? (ii) If so, what are its mechanisms of action?

Personality traits and college students' internet addiction: The mediating roles of general health and self-esteem.

This research aimed to explore the gender-related differences in Internet addiction levels, the associated factors behind Internet addiction, and the mediating roles of general health and self-esteem in the relationship between personality traits and Internet addiction among college students. A total of 318 college students in Iran participating in this study completed sociodemographic information form and self-report measures of Internet addiction, personality traits, general health, and self-esteem. The results showed higher frequencies of low and moderate-severe levels of addiction among female and male students, respectively. Further, younger age, male gender, singleness, high scores on neuroticism, poor general health, and low self-esteem might be linked to Internet addiction. The overall hypothesis that general health and self-esteem mediated the effect of neuroticism on Internet addiction was also supported. Our findings highlighted the necessity of evaluating general health and self-esteem among Internet-addicted students. Further, these variables can be targeted by psychiatrists and psychologists for effective cognitive-behavioral therapy among Internet-addicted students.

Dissociation as a causal pathway from sexual abuse to positive symptoms in the spectrum of psychotic disorders.

BACKGROUND: Although numerous studies have supported the role of childhood maltreatment in the etiology of psychosis, underlying mechanisms have not been well understood yet. The present study aimed to investigate the mediating role of particular forms of dissociation in the relationship between five major types of childhood abuse and psychotic symptoms among patients with schizophrenia spectrum and other psychotic disorders. METHODS: In this cross-sectional correlation study, 70 first-episode psychotic patients and 70 chronic psychotic patients were selected by systematic random sampling (with the sampling interval of 3) from among inpatients and outpatients referring to Baharan Psychiatric hospital, Zahedan, Iran, and were matched based on age, gender, and education level. Moreover, 70 age-, gender-, and education level-matched community controls were recruited from hospital staff and their relatives and friends. All of the participants completed a research interview and questionnaires. Data on experiences of childhood maltreatment, psychosis, dissociation, and demographics were collected and analyzed by SPSS V25 software. RESULTS: The obtained results revealed that the mean scores of sexual abuse, emotional abuse, and physical abuse were higher in psychotic patients than community controls (without any significant difference between first-episode psychotic patients and chronic psychotic patients). Furthermore, the highest mean scores of dissociative experiences belonged to chronic psychotic patients. Multiple-mediation also indicated that absorption and dissociative amnesia played a mediating role in the relationship between sexual abuse and positive symptoms. Moreover, this study demonstrated the role of physical abuse in predicting psychotic symptoms even in the absence of sexual abuse. CONCLUSIONS: This study illustrated specific associations among childhood maltreatment, dissociative experiences, and psychotic symptoms in the clinical population. Thus, to provide appropriate interventions, patients with schizophrenia spectrum and other psychotic disorders were asked about a wide range of possible adverse childhood experiences and dissociative experiences. Nevertheless, further studies using prospective or longitudinal designs need to be carried out to realize the differential contribution of various forms of childhood maltreatment and their potential interactions, more precisely.

Small dense low-density lipoprotein-lowering agents.

Metabolic disorders, including obesity, diabetes, and hyperlipidemia, as well as cardiovascular diseases (CVD), particularly atherosclerosis, are still leading causes of death worldwide. Plasma levels of low-density lipoprotein (LDL) are currently being considered as a critical risk factor for the diseases mentioned above, especially atherosclerosis. Because of the heterogeneous nature of LDL, many studies have already been conducted on its subclasses, especially small dense LDL (sdLDL). According to available evidence, sdLDL levels can be considered as an ideal alternative to LDL levels for monitoring CVD and early diagnosis of atherosclerosis. Recently, several researchers have focused on factors that are able to decrease sdLDL levels and improve health quality. Therefore, the purpose of this study is to describe the production process of sdLDL particles and review the effects of pharmaceutical and dietary agents as well as lifestyle on sdLDL plasma levels. In brief, their mechanisms of action are discussed. Apparently, cholesterol and LDL-lowering compounds are also effective in the reduction of sdLDL levels. In addition, improving lipid profile, especially the reduction of triglyceride levels, appropriate regimen, and lifestyle can decrease sdLDL levels. Therefore, all the aforementioned parameters should be taken into consideration simultaneously in sdLDL levels reducing strategies.

Child maltreatment-related dissociation and its core mediation schemas in patients with borderline personality disorder.

BACKGROUND: From a developmental and pathogenic perspective, child maltreatment is strongly linked to later dissociative symptoms, as ultimate forms of human response to chronic stress. The present study aimed to investigate the mediating role of early maladaptive schemas (EMSs) in the relationship between child maltreatment and dissociation among patients with borderline personality disorder (BPD). METHODS: In this cross-sectional study, a total of 152 BPD patients (men: 52%; women: 48%) with an average age of 29.64 years (standard deviation (SD) = 7.29, range = 18-47) were selected by systematic random sampling from the patients who referred to Baharan psychiatric hospital in Zahedan, Iran, with the sampling interval of 3. The Childhood Trauma Questionnaire-Short Form, Dissociative Experiences Scale, and Young Schema Questionnaire-Short Form 3 were used to assess the patients. Data were analyzed using SPSS v25 software, and the statistical significance level was set at p < 0.05. RESULTS: four main findings were obtained from the present study: (1) Heterogeneity of the levels of dissociation (LOD) in BPD patients; (2) The predicting roles of emotional neglect (EN), vulnerability to harm, and defectiveness/shame schemas in the total DES scores; (3) The vague role of childhood sexual abuse (SA) in developing dissociative symptoms; and (4) The mediating role of the core schemas of vulnerability to harm (ß = 0.28, 95% confidence interval (CI): 0.04, 0.61) and defectiveness/shame (ß = 0.21, 95% CI: 0.008, 0.45) in the relationship between EN and dissociation. CONCLUSIONS: Regarding the heterogeneity of LOD and its crucial role in the successful treatment of BPD patients, it is highly essential to evaluate the present-state dissociation of the patient during the diagnosis process and provide effective interventions to reduce it. The obtained results highlighted the potential role of schema therapy in reducing dissociative responses to emotional stimuli (based on EN), vulnerability to harm, and defectiveness/shame. Nevertheless, psychopathology of dissociation among BPD patients should be further investigated in depth.

Biopsychosocial factors associated with disordered eating behaviors in schizophrenia.

BACKGROUND: Recent hypotheses have suggested that schizophrenic patients are more likely to consume unhealthy foods, causing increased rates of mortality and morbidity associated with metabolic syndrome. This raises the need for more in-depth research on disordered eating behaviors (DEBs) in schizophrenic patients. This study, therefore, aimed to investigate biopsychosocial factors associated with DEBs in schizophrenia. METHODS: In this cross-sectional study, a total of 308 participants (including 83 subjects in the active phase of schizophrenia, 71 subjects in the remission phase of schizophrenia, and 154 control subjects) were recruited through convenience sampling among patients who referred to the Baharan Psychiatric hospital in Zahedan, Iran. Patients were assessed through Eating Attitudes Test (EAT-26), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), and Positive and Negative Syndrome Scale (PANSS). Data were analyzed using SPSS v25 software. Further, the statistical significance level was set at p < 0.05. RESULTS: The prevalence of DEBs was 41.5% in schizophrenic patients (vs. 10.3% in the control group, p = 0.012). No significant difference was observed in the EAT-26 scores based on gender and phases of schizophrenia. According to multiple linear regression analysis, lack of psychosocial rehabilitation, use of atypical antipsychotics, early stages of psychosis, high level of anxiety and depression, expression of more active psychotic symptoms, tobacco smoking, and suffering from type 2 diabetes were all associated with increased development of DEBs among schizophrenic patients. CONCLUSIONS: Since the occurrence of DEBs is independent of different phases of schizophrenia, the risk of DEBs is required to be evaluated during the entire course of schizophrenia especially at earlier stages of schizophrenia. Moreover, the use of psychosocial interventions, treatment of affective disorders (i.e., anxiety and depression), antipsychotic medication switching, treatment of tobacco smoking and type 2 diabetes may reduce the risk of DEBs among schizophrenic patients. However, further investigations are required to prove the actual roles of the above factors in developing DEBs among schizophrenic patients.

The effects of oxidative stress on the development of atherosclerosis.

Atherosclerosis is a cardiovascular disease (CVD) known widely world wide. Several hypothesizes are suggested to be involved in the narrowing of arteries during process of atherogenesis. The oxidative modification hypothesis is related to oxidative and anti-oxidative imbalance and is the most investigated. The aim of this study was to review the role of oxidative stress in atherosclerosis. Furthermore, it describes the roles of oxidative/anti-oxidative enzymes and compounds in the macromolecular and lipoprotein modifications and in triggering inflammatory events. The reactive oxygen (ROS) and reactive nitrogen species (RNS) are the most important endogenous sources produced by non-enzymatic and enzymatic [myeloperoxidase (MPO), nicotinamide adenine dinucleotide phosphate (NADH) oxidase and lipoxygenase (LO)] reactions that may be balanced with anti-oxidative compounds [glutathione (GSH), polyphenols and vitamins] and enzymes [glutathione peroxidase (Gpx), peroxiredoxins (Prdx), superoxide dismutase (SOD) and paraoxonase (PON)]. However, the oxidative and anti-oxidative imbalance causes the involvement of cellular proliferation and migration signaling pathways and macrophage polarization leads to the formation of atherogenic plaques. On the other hand, the immune occurrences and the changes in extra cellular matrix remodeling can develop atherosclerosis process.

Global temporal lobe asymmetry as a semi-quantitative imaging biomarker for temporal lobe epilepsy lateralization: A machine learning classification study.

OBJECTIVE: The purpose of this study was to evaluate the utility of global semi-quantitative analysis via fluorine-18-flurodeoxyglucose positron emission tomography (18F-FDG PET) at lateralizing seizure foci and diagnosing patients with unilateral temporal lobe epilepsy (TLE). METHODS: Seventeen patients with unilateral TLE (11 right TLE and 6 left TLE) were retrospectively selected for semi-quantitative 18F-FDG PET analysis. Twenty-three control subjects with a Mini Mental State Examination (MMSE) score of 29 or greater were selected for comparison. Globally averaged standardized uptake value (gSUVmean) was computed for each temporal lobe. Lateralization indices (LI) and the absolute value of lateralization indices (|LI|) were calculated to assess the degree of asymmetry in each subject. Logistic regression analyses were performed at a probability cutoff of 0.5 to classify TLE patients as left or right TLE and to discriminate patients from control subjects. Receiver operating characteristic (ROC) curves were generated to evaluate the utility of LI and |LI| as classification predictors. The Bland Altman test was used to evaluate the reproducibility of the measurements. RESULTS: There was a statistically significant difference in gSUVmean computed LI between left and right TLE patients (P<0.01). There was no statistically significant difference in |LI| between the patient and control groups (P=0.22). Logistic regression revealed that 82% of TLE patients were lateralized correctly using LI as the sole predictor. The area under the ROC curve (AUC) was 0.80. Logistic regression using |LI| on the combined patient/control population showed a diagnostic accuracy of 65% and an AUC of 0.44. Bland Altman analysis revealed an intra-observer reproducibility of 96% and an inter-observer reproducibility of 96% and 91% on successive trials. CONCLUSION: We conclude that gSUVmean computed LI is a reliable and reproducible measure for predicting seizure lateralization in unilateral TLE patients. However, gSUVmean computed |LI| does not appear to be particularly effective at diagnosing TLE patients from control subjects. Further studies with more patients should investigate other machine learning techniques that combine gSUVmean with other diagnostic predictors.

Normal patterns of regional brain 18F-FDG uptake in normal aging.

OBJECTIVE: Normal aging alters the brain function even in the absence of recognizable structural changes, which can be detected using modern in vivo functional imaging modalities such as fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan. It is highly important to recognize normal age-dependent changes in order to correctly diagnose pathologic states. The goal of the current study was to evaluate the age-related changes in regional brain 18F-FDG uptake in normal healthy population. SUBJECTS AND METHODS: This study was part of the cardiovascular molecular calcification assessed by 18F-sodium fluoride (NaF) (CAMONA) PET/computed tomography (CT) study. This study was approved by the Danish National Committee on Health Research Ethics registered at ClinicalTrials.gov (NCT01724749). Forty normal healthy subjects were prospectively recruited in group A (22-32 years) and B (56-75 years) and underwent 18F-FDG PET/CT. Static images were obtained 180 minutes following 18F-FDG injection. Supratentorial (including individual measurements for frontal, parieto-occipital and temporal lobes) and cerebellar 18F-FDG uptakes were measured by manual placement of region of interest (ROI) over these regions based on predefined criteria for each and standardized uptake value (SUVmean) values were calculated using OsiriX software. RESULTS: The mean ages of the patients in group A was 26.1±3.4 versus 61±4.4 for group B. There were 10 females in group A and 10 females in group B. Mean SUV of cerebellum was 6.80±1.21 for the young subjects compared to 6.08±0.7 among old subjects (independent t-test, P=0.028). Mean SUV of supratentorial brain was 9.14±1.83 for the young subjects compared to 6.92±072 among old subjects (P<0.001). Mean SUV of frontal (9.72±1.97 vs. 7.03±0.69), temporal (7.37±1.52 vs. 5.65±0.68) and parieto-occipital region (10.7±2.28 vs. 7.41±0.79) was higher among young patients (P<0.001). More interestingly, SUVmean of supratentorial brain was significantly higher among female healthy volunteers in both groups (P= 0.025 and 0.047 for group A and B, respectively). CONCLUSION: In conclusion, these findings confirm a significant age dependent reduction of supratentorial 18F-FDG uptake among healthy individuals. However, cerebellum 18F-FDG uptake reduction was not so redundant. Fluorine-18-FDG uptake of all cerebral lobes including frontal, parieto-occipital and temporal decreases with normal aging in a same fashion. Interestingly, among both young and old female subjects, higher uptake was seen in supratentorial brain.