Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells.

CREB [CRE (cAMP-response element)-binding protein] is an important transcription factor that is differentially regulated in cells of various types. We recently reported that RA (retinoic acid) rapidly activates CREB without using RARs (RA receptors) or RXRs (retinoid X receptors) in NHTBE cells (normal human tracheobronchial epithelial cells). However, little is known about the role of RA in the physiological regulation of CREB expression in the early mucous differentiation of NHTBE cells. In the present study, we report that RA up-regulates CREB gene expression and that, using 5\u27-serial deletion promoter analysis and mutagenesis analyses, two Sp1 (specificity protein 1)-binding sites located at nt -217 and -150, which flank the transcription initiation site, are essential for RA induction of CREB gene transcription. Furthermore, we found that CREs located at nt -119 and -98 contributed to basal promoter activity. Interestingly, RA also up-regulated Sp1 in a time- and dose-dependent manner. Knockdown of endogenous Sp1 using siRNA (small interfering RNA) decreased RA-induced CREB gene expression. However, the converse was not true: knockdown of CREB using CREB siRNA did not affect RA-induced Sp1 gene expression. We conclude that RA up-regulates CREB gene expression during the early stage of NHTBE cell differentiation and that RA-inducible Sp1 plays a major role in up-regulating human CREB gene expression. This result implies that co-operation of these two transcription factors plays a crucial role in mediating early events of normal mucous cell differentiation of bronchial epithelial cells

Validity of bag urine culture for predicting urinary tract infections in febrile infants: a paired comparison of urine collection methods

PurposeCatheter urine (CATH-U) and suprapubic aspiration (SPA) are reliable urine collection methods for confirming urinary tract infections (UTI) in infants. However, noninvasive and easily accessible collecting bag urine (CBU) is widely used, despite its high contamination rate. This study investigated the validity of CBU cultures for diagnosing UTIs, using CATH-U culture results as the gold standard.MethodsWe retrospectively analyzed 210 infants, 2- to 24-month-old, who presented to a tertiary care hospital's pediatrics department between September 2008 and August 2013. We reviewed the results of CBU and CATH-U cultures from the same infants.ResultsCBU results, relative to CATH-U culture results (≥104 colony-forming units [CFU]/mL) were widely variable, ranging from no growth to ≥105 CFU/mL. A CBU cutoff value of ≥105 CFU/mL resulted in false-positive and false-negative rates of 18% and 24%, respectively. The probability of a UTI increased when the CBU bacterial count was ≥105/mL for all infants, both uncircumcised male infants and female infants (likelihood ratios [LRs], 4.16, 4.11, and 4.11, respectively). UTIs could not be excluded for female infants with a CBU bacterial density of 104-105 (LR, 1.40). The LRs for predicting UTIs based on a positive dipstick test and a positive urinalysis were 4.19 and 3.11, respectively.ConclusionThe validity of obtaining urine sample from a sterile bag remains questionable. Inconclusive culture results from CBU should be confirmed with a more reliable method

Posterior parietal cortex mediates fear renewal in a novel context

The return of fear following extinction therapy is an important issue associated with the treatment of many fear-related disorders. Fear renewal is a suitable model, with which context-dependent modulation of the fear response can be examined. In this model, any context outside of an extinction context (e.g., novel or familiar contexts) could evoke relapse of the fear response. However, brain regions associated with context-dependent modulation are not fully understood. The posterior parietal cortex (PPC) is considered a center for integrating multisensory information and making decisions. To study its role in the contextual modulation of fear relapse, we reversibly inactivated the PPC in mice before they were exposed to various contexts after extinction training. When muscimol was infused into the PPC, fear renewal was impaired in a novel context, but not in a familiar context. Fear relapses were blocked during optogenetic inhibition of the PPC, only when animals were placed in a novel context. We propose that the neural activity of the PPC is necessary for the relapse of a precise response to an extinguished conditioned stimulus in a novel context. © 2020 The Author(s).1

Paradoxical response during antituberculous therapy in a patient discontinuing infliximab: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Problematic Use of Alcohol and Online Gaming as Coping Strategies During the COVID-19 Pandemic: A Mini Review

The COVID-19 (coronavirus disease 2019) pandemic has dramatically changed our daily lives and activities, including those originally intended to serve for leisure and pleasure. Drinking and online gaming became coping behaviors used to rescue ourselves from the stress and restricted lifestyle during the COVID-19 pandemic. However, frequent drinking and gaming can result in the pathological consequences of addiction. Those affected use the stimuli not to obtain pleasure, but rather to avoid the displeasure induced by stress and previous use, often unsuccessfully. This review aims to provide an overview of recent longitudinal cohort studies on alcohol and gaming use during the COVID-19 pandemic, as well as to analyze how the pandemic has affected alcohol and gaming use. There was a substantial risk of alcohol and online gaming overuse during the lockdown, which may depend on the pandemic's duration or overuse patterns. Previous studies have shown that increased alcohol consumption and online gaming are associated with heightened stress and anxiety levels caused by social isolation/quarantine. Over time, frequent or excessive alcohol consumption and gaming could lead to an increased risk of more serious mental health problems. Every effort should be made to mitigate mental health problems and ensure adequate adaptation to these exceptional circumstances. Therefore, it would be helpful to encourage physical activity, social interaction, and collaboration to facilitate psychological and physical health. © Copyright © 2021 Xu, Park, Kang, Choi and Koo.1

The Aftermath: Post-pandemic Psychiatric Implications of the COVID-19 Pandemic, a South Korean Perspective

The coronavirus disease 2019 (COVID-19) pandemic has disrupted our everyday life. Along with the fear of getting infected or of having loved ones infected, the lifestyle changes and the socioeconomic consequences of the pandemic have profound impact on mental health of the general population. While numerous studies on immediate psychological responses to COVID-19 are being published, there is a lack of discussion on its possible long-term sequelae. In this study, we systematically reviewed and meta-analyzed longitudinal studies that examined mental health of the general population prior to and during the pandemic. Furthermore, we explored the long-term psychiatric implications of the pandemic with data from South Korea. Our analysis showed that the number of suicidal deaths during the pandemic was lower than the previous years in many countries, which is in contrast with the increased depression, anxiety, and psychological distress in the general population in South Korea as well as in other countries. To explain this phenomenon, we propose a possibility of delayed impacts. The post-traumatic stress, long-term consequences of social restrictions, and maladaptive response to the “new normal” are discussed in the paper. COVID-19 being an unprecedented global crisis, more research and international collaboration are needed to understand, to treat, and to prevent its long-term effects on our mental health. Copyright © 2021 Min, Jeong, Kim, Koo and Ahn.1

Social isolation impairs the prefrontal-nucleus accumbens circuit subserving social recognition in mice

Although medial prefrontal cortex (mPFC) is known to play important roles in social behaviors, how early social experiences affect the mPFC and its subcortical circuit remains unclear. We report that mice singly housed (SH) for 8 weeks after weaning show a social recognition deficit, even after 4 weeks of resocialization. In SH mice, prefrontal infralimbic (IL) neurons projecting to the shell region of nucleus accumbens (NAcSh) show decreased excitability compared with group-housed (GH) mice. NAcSh-projecting IL neurons are activated when GH mice encounter a familiar conspecific, which is not observed in SH mice. Chemogenetic inhibition of NAcSh-projecting IL neurons in normal mice impairs social recognition without affecting social preference, whereas activation of these neurons reverses social recognition deficit in SH mice. Our findings demonstrate that early social experience critically affects mPFC IL-NAcSh projection, the activation of which is required for social recognition by encoding information for social familiarity. © 2021 The Author(s)1

Essential Role of SIRT1 Signaling in the Nucleus Accumbens in Cocain and Morphine Action

Sirtuins (SIRTs), class III histone deacetylases, are well characterized for their control of cellular physiology in peripheral tissues, but their influence in brain under normal and pathological conditions remains poorly understood. Here, we establish an essential role for brain reward region. We show that chronic cocain administration increases SIRT1 and SIRT2 expression in the mouse NAc, while chronic morphine administration induces SIRT1 expression alone, with no regulation of all other sirtuin family members observed. Drug induction of SIRT1 and SIRT2 is mediated in part at the transcriptional level via the drug-induced transcription factor ΔFosB and is associated with robust histone modifications at the Sirt1 and Sirt2 genes. Viral-mediated overexpression of SIRT1 or SIRT2 in the NAc enhances the rewarding effects of both cocain and morphine. In contrast, the local knockdown of SIRT1 from the NAc of floxed Sirt1 mice decreases drug reward. Such behavioral effects of SIRT1 occur in concert with its regulation of numerous synaptic proteins in NAc as well as with SIRT1-mediated induction of dendritic spines on NAc medium spiny neurons. These studies establish sirtuins as key mediators of the molecular and cellular plasticity induced by drugs of abuse in NAc, and of the associated behavioral adaptations, and point towards novel signaling pathways involved in drug action