Suppression of excitatory synaptic transmission in the centrolateral amygdala via presynaptic histamine H3 heteroreceptors.

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

Variational dimensions of cingulate cortex functional connectivity and implications in neuropsychiatric disorders.

Significant variations in brain functional connectivity exist in the healthy population, rendering the identification and characterization of their abnormalities in neuropsychiatric disorders difficult. Here, we proposed a new principal component analysis (PCA) approach to study variations in functional connectivity, focusing on major hubs of the salience network and default mode network, namely the anterior and posterior cingulate cortices. We analyzed the intersubject variability of human functional magnetic resonance imaging connectivity obtained from healthy, autistic, and schizophrenic subjects. Utilizing data from 1000 Functional Connectomes Project, COBRE, and ABIDE 1 database, we characterized the normal variations of the cingulate cortices with respect to top PCA dimensions. We showed that functional connectivity variations of the 2 cingulate cortices are constrained, in a parallel manner, by competing or cooperating interactions with different sensorimotor, associative, and limbic networks. In schizophrenic and autistic subjects, diffuse and subtle network changes along the same dimensions were found, which suggest significant behavioral implications of the variational dimensions. Furthermore, we showed that individual dynamic functional connectivity tends to fluctuate along the principal components of connectivity variations across individuals. Our results demonstrate the strength of this new approach in addressing the intrinsic variations of network connectivity in human brain and identifying their subtle changes in neuropsychiatric disorders.

Long-range monosynaptic inputs targeting apical and basal dendrites of primary motor cortex deep output neurons.

The primary motor cortex (M1) integrates various long-range signals from other brain regions for the learning and execution of goal-directed movements. How the different inputs target the distinct apical and basal dendrites of M1 pyramidal neurons is crucial in understanding the functions of M1, but the detailed connectivity pattern is still largely unknown. Here, by combining cre-dependent rabies virus tracing, layer-specific chemical retrograde tracing, optogenetic stimulation, and electrophysiological recording, we mapped all long-range monosynaptic inputs to M1 deep output neurons in layer 5 (L5) in mice. We revealed that most upstream areas innervate both dendritic compartments concurrently. These include the sensory cortices, higher motor cortices, sensory and motor thalamus, association cortices, as well as many subcortical nuclei. Furthermore, the dichotomous inputs arise mostly from spatially segregated neuronal subpopulations within an upstream nucleus, and even in the case of an individual cortical layer. Therefore, these input areas could serve as both feedforward and feedback sources albeit via different subpopulations. Taken together, our findings revealed a previously unknown and highly intricate synaptic input pattern of M1L5 neurons, which implicates that the dendritic computations carried out by these neurons during motor execution or learning are far more complicated than we currently understand.

Comparison of a novel lateral-flow device to galactomannan assay at different time periods for detections of invasive aspergillosis.

PURPOSE: To compare a lateral-flow device (LFD) method to the galactomannan assay (GM) for the diagnosis of invasive aspergillosis (IA). METHODS: First, 20 GM-positive serum samples stored for two years were retested with both the GM and LFD assays. Second, 153 serum samples from 91 immunocompromised patients suspected of having IA were tested prospectively, including 56 hematologic malignancies and 35 chronic illnesses with steroid therapy. RESULTS: For the twenty GM-positive stored samples, only ten were positive for the repeated GM assay and none were positive for IA according to the LFD test. The concordance of the LDF with the GM test was 79.81% (83/104) if both tests were performed on the sample collection day, with the rate reducing to 67.65% (23/34) (p < 0.05) if the LFD test was performed 2-7 days after the GM test. Furthermore, there was a significant difference in the discrepancy between the GM and LFD tests between previous and no anti-mold exposure subgroups (33.33% vs. 12.31%, p < 0.01). The sensitivity and specificity of the GM test were 89.65% and 98.66%, 68.96%, and 78.67% for the LFD assay. CONCLUSION: Serum samples that have been stored long term are not suitable for re-testing with the GM or LFD assay. There was a strong correlation between the LFD and GM assay results if the tests were performed on the same day, however, this decreased if the samples were stored for more than 2 days. Additionally, previous exposure to antibiotics and/or antifungal therapy could influence the LFD results, leading to discrepancies with the GM test results.

The involvement of nuclear factor-κB in astroprotection against ischemia-reperfusion injury by ischemia-preconditioned neurons.

Ischemic preconditioned (IP) neurons protect astrocytes against ischemia/reperfusion (I/R)-induced injury by inhibiting oxidative stress. However, the relevant mechanisms are unknown. Based on the role of nuclear factor-κB (NF-κB) in cell survival and adaption to oxidative stress, we hypothesized that NF-κB might be associated with astroprotection induced by IP neurons via upregulation of antioxidant enzymes. Here, we investigated the effects of IP neurons on NF-κB activation, cell viability, reactive oxygen species (ROS), expression of antioxidant enzymes, erythropoietin (EPO), and tumor necrosis factor α (TNF-α), in the presence or absence of BAY11-7082 (an NF-κB inhibitor), anti-EPO, and anti-TNF-α antibodies, in astrocytes treated with or without I/R. We found that IP neurons could keep NF-κB activation at a relatively higher but beneficial level, and in turn, upregulated the activity of antioxidant enzymes and hence enhanced cell viability and reduced ROS in I/R treated astrocytes. The results collectively indicated that IP neurons are able to significantly inhibit the I/R-induced NF-κB overactivation, probably via EPO and TNF-α, being essential for IP neuron-induced astroprotection under the conditions of I/R. We concluded that NF-κB-mediated antioxidative stress is one of the mechanisms by which IP neurons protect astrocytes against I/R injury.

Dopamine receptors mediate strategy abandoning via modulation of a specific prelimbic cortex-nucleus accumbens pathway in mice.

The ability to abandon old strategies and adopt new ones is essential for survival in a constantly changing environment. While previous studies suggest the importance of the prefrontal cortex and some subcortical areas in the generation of strategy-switching flexibility, the fine neural circuitry and receptor mechanisms involved are not fully understood. In this study, we showed that optogenetic excitation and inhibition of the prelimbic cortex-nucleus accumbens (NAc) pathway in the mouse respectively enhances and suppresses strategy-switching ability in a cross-modal spatial-egocentric task. This ability is dependent on an intact dopaminergic tone in the NAc, as local dopamine denervation impaired the performance of the animal in the switching of tasks. In addition, based on a brain-slice preparation obtained from Drd2-EGFP BAC transgenic mice, we demonstrated direct innervation of D2 receptor-expressing medium spiny neurons (D2-MSNs) in the NAc by prelimbic cortical neurons, which is under the regulation by presynaptic dopamine receptors. While presynaptic D1-type receptor activation enhances the glutamatergic transmission from the prelimbic cortex to D2-MSNs, D2-type receptor activation suppresses this synaptic connection. Furthermore, manipulation of this pathway by optogenetic activation or administration of a D1-type agonist or a D2-type antagonist could restore impaired task-switching flexibility in mice with local NAc dopamine depletion; this restoration is consistent with the effects of knocking down the expression of specific dopamine receptors in the pathway. Our results point to a critical role of a specific prelimbic cortex-NAc subpathway in mediating strategy abandoning, allowing the switching from one strategy to another in problem solving.

Stereoselective Access to Polyfunctionalized Nine-Membered Heterocycles by Sequential Gold and Palladium Catalysis.

We report herein a gold and palladium sequential catalysis system to access furan-fused nine-membered heterocycles in high efficiency and enantioselectivity. In this one-pot procedure, easily accessible enynamides undergo cyclization to generate azadienes in situ that participate in enantioselective formal [5+4] cycloaddition with vinyl ethylene carbonates. Conformation-controlled highly diastereoselective derivatizations of these medium-sized rings, coupled with oxidative furan cleavage, have enabled the access to diverse densely-functionalized nine-membered lactams.

Tandem Catalytic Indolization/Enantioconvergent Substitution of Alcohols by Borrowing Hydrogen to Access Tricyclic Indoles.

An efficient tandem catalysis method is achieved for the direct conversion of alcohol-containing alkynyl anilines to valuable chiral 2,3-fused tricyclic indoles. This method relies on a tandem indolization followed by enantioconvergent substitution of alcohols via borrowing hydrogen to construct two rings in one step, enabled by relay and cooperative catalysis of a chiral iridium complex with a chiral phosphoric acid. Highly diastereoselective transformations of the tricyclic indole products also provide efficient access to a diverse array of complex polycyclic indoline compounds.

Hepcidin and its therapeutic potential in neurodegenerative disorders.

Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich's ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron-related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood-brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron-associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.

Attenuation of intermittent hypoxia-induced apoptosis and fibrosis in pulmonary tissues via suppression of ER stress activation.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis and endothelial apoptosis in pulmonary tissues. Chronic intermittent hypoxia (IH) is considered to be the primary player in OSA, but the mechanisms underlying its effect on pulmonary tissues are unknown. Endoplasmic reticulum (ER) stress induced by IH treatment plays an important role in accelerating the process of fibrosis and induction of apoptosis. METHODS: Mice were placed in IH chambers for 4 weeks with an oscillating oxygen (O2) concentration between 5 and 21%, cycling every 90s for 8 h daily. Mice were randomly divided into four groups: control group (normal oxygen), tauroursodeoxycholic acid (TUDCA) group (normal oxygen intraperitoneally injected with TUDCA), IH group and IH + TUDCA group. After 4 weeks, the proteins in three branch signaling pathways of ER stress, including protein kinase RNA (PKR)-like/Pancreatic ER kinase (PERK), activating transcription factor 6 (ATF-6) and inositol-requiring enzyme 1 (IRE-1), were evaluated. The cleaved caspase-3, caspase-12 and TUNNEL staining was assessed. Furthermore, the expression of transforming growth factor-ß1 (TGF-ß1) and thrombospondin-1(TSP-1), two extracellular matrix proteins that play critical role in fibrosis, were examined. Finally, Masson's trichrome staining was performed to detect the expression of collagen. RESULTS: After 4 weeks of IH treatment, the expressions of two ER stress markers, glucose regulated protein-78 (Grp78) and transcription factor C/EBP homologous protein (CHOP) were increased which was prevented by administration of the ER stress attenuator, TUDCA. The expressions of PERK, but not those of ATF-6 and IRE-1, were increased. The effects of IH were accompanied by an increased number of apoptotic cells and increased expressions of cleaved caspase-3 and caspase-12 in pulmonary tissues. In addition, histological examination suggested the presence of fibrosis after chronic IH treatment, indicated by increased expression of collagen, which was associated with the up-regulation of TGF-ß1 and TSP-1 that are known to promote fibrosis. Similarly, TUDCA could reduce the extent of fibrotic area and the expression levels of these proteins. CONCLUSIONS: It reveals the roles of ER stress, especially the PERK pathway, in IH induced apoptosis and fibrosis in pulmonary tissues that might underlie the pulmonary complications observed in OSA.

Factors that affect the health status of health care providers-A cross-sectional design.

AIM: To explore the factors that affect the health status of health care providers. BACKGROUND: There is a lack of studies that address the stress, resilience, social support and health status of health care providers. METHODS: Using a cross-sectional study design, 500 participants were recruited from three hospitals which were operated by one entity in southern Taiwan. Data were collected with structured questionnaires. A logistic regression analysis was performed to explore the factors that might affect the health status of health care providers. RESULTS: Among the 500 health care providers, 345 were healthy and 155 were unhealthy. Health status was not significantly correlated with any demographic characteristics, but was significantly correlated with work stress, resilience and social support, with work stress being an important factor influencing the health status of health care providers. CONCLUSIONS: Health care providers with health issues had higher work stress, less resilience and less social support than did healthy medical personnel. Moreover, work stress was the main factor affecting the health of health care providers. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators should conduct a series of health management programmes to identify high-risk employees who might need assistance. Such programmes promoting healthy workplaces are necessary, as well as studies that examine the effectiveness of such strategies.

Regulating ferroportin-1 and transferrin receptor-1 expression: A novel function of hydrogen sulfide.

Hydrogen sulfide (H2 S) has a significant effect on the regulation of interleukin-6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) activities, while IL-6 directly regulates hepcidin expression via STAT3. We therefore hypothesized that H 2 S has a role in body iron homeostasis by regulating the expression of iron transport proteins via the IL-6/STAT3/Hepcidin pathway. Here, we investigated the effects of two H 2 S donors sodium hydrosulfide and GYY4137 on the expression of ferroportin-1 (Fpn1), transferrin receptor-1 (TfR1), hepcidin, IL-6 and pSTAT3 in the spleen of mice in vivo and peritoneal macrophage in vitro. We also examined the effects of H 2 S on serum iron, transferrin saturation, and ferritin light chain contents in the spleen, and on nitrite content, nuclear factor erythroid 2-related factor-2 (Nrf2) and iron regulatory protein 1 (IRP1) in the macrophages. We demonstrated that H 2 S regulates the expression of TfR1 and Fpn1 in the spleen in vivo and in peritoneal macrophages in vitro predominantly via the IL-6/pSTAT3/hepcidin pathway, under the conditions of inflammation induced by lipopolysaccharides. We also provide evidence that under uninflamed conditions, the regulation of Fpn1 and TfR1 expression by H 2 S, both in vivo and in vitro, are mediated by the nitric oxide (NO)/Nrf2 and iron regulatory protein/iron responsive element pathways, respectively, which are independent of IL-6/pSTAT3/hepcidin signals. These findings show that H 2 S is a key player in iron homeostasis under not only the inflamed conditions but also uninflamed conditions.

Cystathionine ß-synthase is required for body iron homeostasis.

Cystathionine ß-synthase (CBS) catalyzes the transsulfuration pathway and contributes, among other functions, to the generation of hydrogen sulfide. In view of the exceptionally high expression of CBS in the liver and the common interleukin-6 pathway used in the regulatory systems of hydrogen sulfide and hepcidin, we speculate that CBS is involved in body iron homeostasis. We found that CBS knockout (CBS-/- ) mice exhibited anemia and a significant increase in iron content in the serum, liver, spleen, and heart, along with severe damage to the liver, displaying a hemochromatosis-like phenotype. A high level of hepatic and serum hepcidin was also found. A major cause of the systemic iron overload is the reduced iron usage due to suppressed erythropoiesis, which is consistent with an increase in interleukin-6 and reduced expression of erythropoietin. Importantly, in the liver, absence of CBS caused both a reduction in the transcriptional factor nuclear factor erythroid 2-related factor-2 and an up-regulation of hepcidin that led to a decrease in the iron export protein ferroportin 1. The resulting suppression of iron export exacerbates iron retention, causing damage to hepatocytes. Finally, administration of CBS-overexpressing adenovirus into CBS mutant mice could partially reverse the iron-related phenotype. CONCLUSION: Our findings point to a critical role of CBS in iron homeostasis of the body, and the liver in particular; it is likely that a hemochromatosis-like phenotype in patients can be induced by aberration not only in the expression of key molecules in the hepcidin pathway but also of those related to CBS. (Hepatology 2018;67:21-35).

On the difficulty of finding one's place: A qualitative study of new nurses' processes of growth in the workplace.

AIMS AND OBJECTIVE: To explore new nurses' processes of growth in the workplace in order to understand the challenges they face. BACKGROUND: Quantitative and qualitative research to date has not adequately explored the complex ways in which initial work experiences may shape new nurses' very high quit rate and, consequently, impact the long-term nursing shortage in Taiwan. DESIGN/METHODS: We conducted in-depth interviews with new nurses to explore their professional development, including the challenges they faced, and their feelings about staying or quitting. Twenty newly registered nurses who had worked in a hospital setting full-time for a year or less in two southern Taiwan medical centres were interviewed. Data were collected from March-November 2016. EQUATOR guidelines were followed, using the COREQ checklist. RESULTS: Interview transcripts were analysed and coded; three stages of growth were discovered: Feeling disillusioned and shocked, Gaining experiential knowledge and Making a place for oneself. Most nurses (n = 18/20) went through these three stages within 9 months and continued to work in nursing at follow-up 2 years later. CONCLUSIONS: Job continuity was contingent upon new nurses' enduring a painful process of adjustment in the first two stages when new nurses were unsure of themselves and their interactions with preceptors were wrought with social tensions. New nurse development and retention efforts should make explicit the possibility of these tensions and how to deal with them. RELEVANCE TO CLINICAL PRACTICE: A better understanding of new nurses' growth processes and adjustment pains can help refocus professional development and retention efforts towards how new nurses can succeed in finding a place for themselves.

Fasting up-regulates ferroportin 1 expression via a Ghrelin/GHSR/MAPK signaling pathway.

The significant positive correlation between ghrelin and iron and hepcidin levels in the plasma of children with iron deficiency anemia prompted us to hypothesize that ghrelin may affect iron metabolism. Here, we investigated the effects of fasting or ghrelin on the expression of hepcidin, ferroportin 1 (Fpn1), transferrin receptor 1 (TfR1), ferritin light chain (Ft-L) proteins, and ghrelin, and also hormone secretagogue receptor 1 alpha (GHSR1α) and ghrelin O-acyltransferase (GOAT) mRNAs in the spleen and/or macrophage. We demonstrated that fasting induces a significant increase in the expression of ghrelin, GHSR1α, GOAT, and hepcidin mRNAs, as well as Ft-L and Fpn1 but not TfR1 proteins in the spleens of mice in vivo. Similar to the effects of fasting on the spleen, ghrelin induced a significant increase in the expression of Ft-L and Fpn1 but not TfR1 proteins in macrophages in vitro. In addition, ghrelin was found to induce a significant enhancement in phosphorylation of ERK as well as translocation of pERK from the cytosol to nuclei. Furthermore, the increased pERK and Fpn1 induced by ghrelin was demonstrated to be preventable by pre-treatment with either GHSR1α antagonist or pERK inhibitor. Our findings support the hypothesis that fasting upregulates Fpn1 expression, probably via a ghrelin/GHSR/MAPK signaling pathway.

Transcriptome analysis unravels an ethylene response factor involved in regulating fruit ripening in pear.

Ethylene response factor (ERF) has been widely studied in regulating fruit ripening in tomato, apple, banana and kiwifruit, but little is known in pear. In this study 1-methylcyclopropene (1-MCP) treatment, an inhibitor of ethylene perception, was conducted at approximately 30 days before harvest to delay fruit ripening in a climacteric white pear cultivar Yali. Transcriptome libraries were constructed and sequenced in pre-ripening, ripening, and 1-MCP treated fruits. Data analysis showed that 73 candidate genes related to fruit ripening were induced by 1-MCP, among which two were positively related, namely 1-aminocyclopropane-1-carboxyla oxidase and an ERF gene (designated as ACO54 and ERF24). Transient transformations in pear fruit revealed that over-expression of ACO54 enhance transcription level of ERF24 and most ripening-related genes. Meanwhile, over-expression of ERF24 raises expression level of ACO54 and partially ripening-related genes. Moreover, dual-luciferase and yeast-one-hybrid assays unravel an interaction between ERF24 and the ACO54 promoter. Therefore, the ERF24 could directly regulate ACO54 expression by binding to its promoter. These results suggested that the first identified ERF24 is involved in regulating fruit ripening in Chinese white pear.

Differential interaction between iron and mutant alpha-synuclein causes distinctive Parkinsonian phenotypes in Drosophila.

Alpha-synuclein aggregation is the central hallmark of both sporadic and familial Parkinson's disease (PD). Patients with different PD-causing genetic defects of alpha-synuclein usually show distinctive clinical features that are atypical to sporadic PD. Iron accumulation is invariably found in PD. Recent studies showed that mutant and wild-type alpha-synuclein may have differential interaction with iron and mutant alpha-synuclein toxicity could be preferentially exacerbated by iron. We hence hypothesized that iron overload could selectively influence mutant alpha-synuclein toxicity and disease phenotypes. To test the hypothesis, we investigated if Drosophila melanogaster over-expressing A53T, A30P, and wild-type (WT) alpha-synuclein have different responses to iron treatment. We showed that iron treatment induced similar reduction of survival rate in all flies but induced a more severe motor decline in A53T and A30P mutant alpha-synuclein expressing flies, suggesting interaction between mutant alpha-synuclein and iron. Although no significant difference in total head iron content was found among these flies, we demonstrated that iron treatment induced selective DA neuron loss in motor-related PPM3 cluster only in the flies that express A53T and A30P mutant alpha-synuclein. We provided the first in vivo evidence that iron overload could induce distinctive neuropathology and disease phenotypes in mutant but not WT alpha-synuclein expressing flies, providing insights to the cause of clinical features selectively exhibited by mutant alpha-synuclein carriers.

The multi-level impact of chronic intermittent hypoxia on central auditory processing.

During hypoxia, the tissues do not obtain adequate oxygen. Chronic hypoxia can lead to many health problems. A relatively common cause of chronic hypoxia is sleep apnea. Sleep apnea is a sleep breathing disorder that affects 3-7% of the population. During sleep, the patient's breathing starts and stops. This can lead to hypertension, attention deficits, and hearing disorders. In this study, we apply an established chronic intermittent hypoxemia (CIH) model of sleep apnea to study its impact on auditory processing. Adult rats were reared for seven days during sleeping hours in a gas chamber with oxygen level cycled between 10% and 21% (normal atmosphere) every 90s. During awake hours, the subjects were housed in standard conditions with normal atmosphere. CIH treatment significantly reduces arterial oxygen partial pressure and oxygen saturation during sleeping hours (relative to controls). After treatment, subjects underwent functional magnetic resonance imaging (fMRI) with broadband sound stimulation. Responses are observed in major auditory centers in all subjects, including the auditory cortex (AC) and auditory midbrain. fMRI signals from the AC are statistically significantly increased after CIH by 0.13% in the contralateral hemisphere and 0.10% in the ipsilateral hemisphere. In contrast, signals from the lateral lemniscus of the midbrain are significantly reduced by 0.39%. Signals from the neighboring inferior colliculus of the midbrain are relatively unaffected. Chronic hypoxia affects multiple levels of the auditory system and these changes are likely related to hearing disorders associated with sleep apnea.

Berberine Alleviates Oxidative Stress in Islets of Diabetic Mice by Inhibiting miR-106b Expression and Up-Regulating SIRT1.

Mounting studies have indicated the role of berberine, SIRT1, and oxidative stress in diabetes, respectively. However, few studies have demonstrated their correlation and regulation function in diabetes. Therefore, the protective effect of berberine in diabetic and the underlying core mechanism were investigated in the current study. Diabetic mice model in vivo were established. Mouse pancreatic beta-cell line NIT-1 cells were treated with 30 mM high glucose to induce diabetic condition in vitro. Serum biochemical parameters (glucose, total cholesterol, and triglycerides) were detected. Oxidative stress indicators (MDA, SOD1), along with miR-106b and SIRT1 expression in islets and cells were also assessed. Direct targeting relationship between miR-106b and SIRT1 was discussed by dual luciferase reporter gene assay. Diabetic model in vivo and in vitro were both established successfully. The expression of serum biochemical parameters was increased, and oxidative stress parameters, and miR-106b, SIRT1 were abnormally expressed in diabetic mice and NIT-1 cells. Meanwhile, berberine could alleviate oxidative stress injury in diabetic progression. Through dual luciferase reporter gene assay, we found that SIRT1 was a target gene of miR-106b. In addition, miR-106b over-expression could reverse the protection of berberine in NIT-1 cells against from oxidative stress induced by high glucose. Berberine could attenuate oxidative stress of diabetic mice at least partly through miR-106b/SIRT1 pathway and affecting the function of islets, which might be beneficial in reducing the cardiovascular risk factors in diabetes. J. Cell. Biochem. 118: 4349-4357, 2017. © 2017 Wiley Periodicals, Inc.

The effects of nursing preceptorship on new nurses' competence, professional socialization, job satisfaction and retention: A systematic review.

AIMS: The aim of this study was to determine the effects of nursing preceptorship on the competence, job satisfaction, professional socialization and retention of new nurses. BACKGROUND: Although studies have focused on the effects of nursing preceptorship on new nurses' competence and retention, a systematic review of the overall effects is lacking. DESIGN: A quantitative systematic review. DATA SOURCES: Five English/Chinese databases were searched for original articles published before June 2015 and only six articles published between 2001-2014 were included in the final analysis. REVIEW METHODS: Joanna Briggs Methodology was used to process one randomization control trial, one quasi-experimental study and four observational studies. Two appraisers independently reviewed each study using the standardized critical appraisal tools from the Joanna Briggs Institute. RESULTS: The most adopted preceptorship was a fixed preceptor/preceptee model and one-on-one for 1-3-month duration. It showed that new nurses' overall competence increased significantly due to preceptorship. Only a few studies explored the effects of preceptorship on the job satisfaction and professional socialization of new nurses. Clear conclusions regarding the effect of preceptorship on nurses' retention rate could not be made because of inconsistent time points for calculation and a lack of control groups in the study design. CONCLUSIONS: Preceptorship can improve new nurses' nursing competence; however, more studies are needed to ascertain its effects on new nurses' retention rates, job satisfaction and professional socialization to promote nursing care quality and resolve nursing shortages.