A fatal septic shock caused by Capnocytophaga gingivalis potentially associated with COVID-19: A case report.

Background: Capnocytophaga spp. is associated with fulminant sepsis, particularly in those with immunosuppression. We here report a rare case of fatal fulminant septic shock caused by C. gingivalis, concurrent with COVID-19. Case Presentation: A Japanese woman developed septic shock, which led to her death. Polymerase chain reaction (PCR) testing of the respiratory specimen was positive for SARS-CoV-2, and a CT scan of the chests revealed bilateral ground glass opacities. The blood cultures identified C. gingivalis. The patient had rheumatoid arthritis and was taking prednisone orally. There were no splenic abnormalities shown on the CT scan. Conclusion: A rare case of fulminant septic shock caused by C. gingivalis, together with COVID-19 was identified. The precise pathogenesis of this combination, together with the best treatment option should be sought by further studies.

Molecular Mechanisms of Inhibitory Effects of Bovine Lactoferrin on Invasion of Oral Squamous Cell Carcinoma.

Lactoferrin (LF), an iron-binding glycoprotein, has been reported to have anticancer properties. However, the molecular mechanisms behind its anticancer effects on oral squamous cell carcinoma (OSCC) have not yet been elucidated. Therefore, we aimed to clarify the effects of LF on invasion of OSCC, and its underlying molecular mechanism. OSCC cell lines, HSC2 and HOC313, were treated with bovine LF (bLF). The effects of bLF on cell invasion were examined by a chamber migration assay, wound healing assay, and Boyden chamber method with a basement-membrane-analogue. Expression levels of MMP-1, MMP-3, and AP-1 were examined using RT-PCR, qRT-PCR, and western blotting. Roles of LRP1, a receptor of bLF, on cell invasion were analyzed using siLRP1 knockdown cells. Furthermore, to clarify the importance of LRP1 in invasion, the effects of bLF on tPA-induced invasion of OSCC cells were examined. The invasion assays showed that bLF suppressed invasion of the OSCC cells. Moreover, bLF down-regulated AP-1, and resulted in reductions of MMP-1 and MMP-3. With SiLRP1 knockdown, OSCC cells failed to induce their invasion, and bLF was not able to exert its effects on invasion. Furthermore, bLF remarkably inhibited tPA-induced cell invasion. These findings suggest the importance of LRP1 in bLF-suppressed invasion of OSCC cells via the reduction of AP-1 and MMP production.

Deprescribing antacids after the diagnosis of Clostridioides difficile infection: A single-center observational study.

Overuse of antacids is associated with the development and recurrence of Clostridioides difficile infection (CDI). Discontinuation of unnecessary antacids for CDI management is advocated; however, the clinical pervasiveness on the discontinuation of antacids remains unclear. We conducted a single-center retrospective observational study to determine the rate of antacid discontinuation following CDI diagnosis. Among 51 patients (58 infections; median age 76.5 years, range 69-82; 53.5% women) treated with antimicrobials against C. difficile, 41 had been treated with antacids, and of these, 18 exhibited no indication for antacid administration. However, none had discontinued antacid use. While CDI provides an opportunity for antacid stewardship, it is not implemented in clinical practice. In addition to the efforts of individual clinicians, the dissemination of knowledge of the indications and side effects of antacids, establishment of a multidisciplinary support system, and creation and implementation of a clinical stewardship pathway are necessary to increase the deprescription of antacids in patients with CDI.

Bovine lactoferrin reverses programming of epithelial-to-mesenchymal transition to mesenchymal-to-epithelial transition in oral squamous cell carcinoma.

Epithelial-to-mesenchymal transition (EMT) is a biological process of invasion and metastasis in cancers, including in oral squamous cell carcinoma (OSCC). However, an effective anticancer drug that directly targets EMT has not yet been discovered. Therefore, we aimed to investigate the repressive effects of bovine lactoferrin (bLF) on EMT to achieve mesenchymal-to-epithelial transition (MET) in OSCC. OSCC cell lines, HOC313 (EMT-induced) and SCCVII (without EMT induction), were treated with bLF. The effects of bLF on EMT in OSCC were identified histologically by haematoxylin and eosin staining and observed morphologically and immunohistochemically using an anti-E-cadherin antibody. Expression levels of E-cadherin and vimentin were investigated using RT-PCR and western blotting. Immuno-expression of E-cadherin was examined in vivo in tumour tissues of C3H/HeN mice, transplanted with SCCVII cells, with or without bLF administration. We found that bLF changed the spindle-like mesenchymal cells to cuboidal-like epithelial cells and enhanced the affinity of membrane-bound E-cadherin in HOC313 cells. The transformation of EMT-MET in HOC313 cells was confirmed by the upregulation of E-cadherin and suppression of vimentin. Moreover, bLF suppressed TWIST expression through downregulation of ERK1/2 phosphorylation. Additionally, the inhibition tumour cell infiltration and increase in E-cadherin expression were observed in xenografts of the mice orally administered with bLF. Thus, based on the results from in vitro and in vivo studies, we concluded that bLF caused the restoration of epithelial properties through MET. Importantly, this finding is novel and is the first report indicating that bLF inhibited EMT and induced MET in OSCC, suggesting that bLF may provide a novel therapeutic strategy in OSCC.

Natural reduced water suppressed anxiety and protected the heightened oxidative stress in rats.

BACKGROUND: In Japan, the effects of reduced water, such as hydrogen-rich electrolyzed reduced water and natural reduced water, like Hita Tenryosui water®, have been examined. The purpose of the present study was to identify the role of natural reduced water in anxiety and blood biochemical analysis. MATERIALS AND METHODS: Natural reduced water and distilled water were administered to rats for 180 consecutive days, and their effect on anxiety-like behavior and depression was examined by using elevated plus maze, light/dark, forced swimming, and conditioned fear tests. Before and after administration of natural reduced or distilled water, we performed blood and urine analyses. RESULTS: Natural reduced water exhibited anxiolytic-like effects in the conditioned fear and elevated plus maze tests. The mean levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the natural reduced water were significantly lower than the distilled water group. Natural reduced water group also showed decrease in blood-urea nitrogen levels compared with the distilled water group. CONCLUSION: These results indicate that natural reduced water may decrease anxiety-related behaviors and prevent heightened oxidative stress.

Gender differences in automatic thoughts and cortisol and alpha-amylase responses to acute psychosocial stress in patients with obsessive-compulsive personality disorder.

INTRODUCTION: Obsessive-compulsive personality disorder (OCPD) has a pervasive pattern of preoccupation with orderliness, perfection, and mental and interpersonal control at the expense of flexibility, openness, and efficiency. The aims of the present study were to explore the relationship between OCPD and psychological stress and psychological tests. METHODS: We evaluated 63 OCPD patients and 107 healthy controls (HCs). We collected saliva samples from patients and controls before and after a social stress procedure, the Trier Social Stress Test (TSST), to measure the concentrations of salivary alpha-amylase (sAA) and salivary cortisol. The Childhood Trauma Questionnaire (CTQ), Profile of Mood State (POMS), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Social Adaptation Self-Evaluation Scale (SASS), and Depression and Anxiety Cognition Scale (DACS) were administered to patients and HCs. RESULTS: Following TSST exposure, the salivary amylase and cortisol levels were significantly decreased in male patients compared with controls. Additionally, OCPD patients had higher CTQ, POMS, STAI, and BDI scores than HCs and exhibited significantly higher anxiety and depressive states. OCPD patients scored higher on future denial and threat prediction as per the DACS tool. According to a stepwise regression analysis, STAI, POMS, and salivary cortisol responses were independent predictors of OCPD. CONCLUSIONS: Our results suggested that attenuated sympathetic and parasympathetic reactivity in male OCPD patients occurs along with attenuated salivary amylase and cortisol responses to the TSST. In addition, there was a significant difference between OCPD patients and HCs in child trauma, mood, anxiety, and cognition. The finding support the modeling role of cortisol (20min) on the relationships between STAI trait and depression among OCPD.

Different functioning of prefrontal cortex predicts treatment response after a selective serotonin reuptake inhibitor treatment in patients with major depression.

BACKGROUND: Major depressive disorder (MDD) is often resistant to treatment with usual approaches. Patients with MDD have shown hypofunction of the frontotemporal cortex in verbal fluency test (VFT)-related near-infrared spectroscopy (NIRS). METHODS: We examined whether the reactions to drug treatment in treatment-naive patients with MDD could be predicted by NIRS outcomes at the initial investigation. All subjects underwent psychological testing to determine levels of anxiety and depression. VFT was used to examine the functioning of the frontotemporal lobes. We administered selective serotonin reuptake inhibitors (SSRIs) for 12 weeks. Subjects included 28 patients with MDD with response to SSRIs (Response group), 19 with no response (Non-Response group), and 63 age-, sex-, and education years-matched healthy controls (HC). RESULTS: We found in the frontotemporal region that hemodynamic responses were significantly smaller in patients with Response and Non-Response groups than in HC before treatment. We also found in the medial frontal region that hemodynamic responses were significantly larger in patients with Response groups than in patients with Non-Response group before treatment. Patients with MDD scored significantly higher anxiety and depressive states than those in HC on several measures. The Response and Non-Response groups also had higher scores in future denial, threat prediction, self-denial, past denial, and interpersonal threat sections of Anxiety Cognition Scale (DACS). According to the stepwise regression analysis, one variable was determined as independent predictors of response: confusion (Post-POMS). LIMITATIONS: The number of patients and healthy controls was relatively small, and we will increase the number of participants in future studies. NIRS has reduced spatial resolution, which confuses the identification of the measurement position when using NIRS alone. CONCLUSION: Cognitive vulnerabilities are associated with predictors of SSRI treatment response. Different hemodynamic activities in the frontotemporal cortex predict response to SSRI treatment in MDD.

Sex determines cortisol and alpha-amylase responses to acute physical and psychosocial stress in patients with avoidant personality disorder.

INTRODUCTIONS: Avoidant personality disorder (AVPD) has excessive and pervasive anxiety and discomfort in social situations. The aims of this study were to explore the relationship between AVPD and physical and psychological stress and psychological tests. METHODS: We evaluated 93 AVPD patients and 355 nonpatient controls by salivary amylase and cortisol responses during exposure to the Trier Social Stress Test (TSST) and electrical stimulation stress. Spielberger state-trait anxiety inventory (STAI), Profile of Mood State (POMS), Beck Depression Inventory (BDI), Depression and Anxiety Cognition Scale (DACS), and Childhood Trauma Questionnaire (CTQ) were administered. RESULTS: Following electrical stimulation, salivary cortisol levels in female AVPD decreased significantly less than that in female's controls, but salivary cortisol levels did not show a difference between male AVPD patients and controls. Salivary alpha-amylase (sAA) levels did not show a difference between females or male AVPD patients and controls. Following TSST exposure, sAA levels did not show a difference between females or male AVPD patients and controls. Salivary cortisol levels did not show a difference between females or male AVPD patients and controls. In the AVPD patients, POMS scores were significantly higher compared with the controls. STAI, BDI, DACS scores, and CTQ significantly increased in the AVPD patients compared with the controls. LF in heart rate variability in AVPD significantly increased more compared with controls. CONCLUSIONS: These results suggest that heightened sympathetic reactivity in female AVPD co-occurs with attenuated salivary cortisol responses to electric stimulation stress and there is a significant difference between AVPD and controls in mood, anxiety, social cognition, and automatic nerve systems.

Hyperfunction of left lateral prefrontal cortex and automatic thoughts in social anxiety disorder: A near-infrared spectroscopy study.

BACKGROUND: Patients with social anxiety disorder (SAD) experience unusual fear in normal social situations. The verbal fluency task (VFT) was administered while subjects were undergoing near-infrared spectroscopy (NIRS) scanning. The purpose of VFT was to examine the functions of the frontal and temporal lobes. METHODS: Subjects included 145 drug-naïve patients with SAD and 152 healthy controls (HCs). All subjects underwent psychological testing to determine levels of anxiety and depression and to evaluate cognition. RESULTS: The scores of patients with SAD indicated significantly higher anxiety and depressive states than those in HCs on several measures: Leibowitz Social Anxiety Scale (LSAS), Profile of Mood States (POMS), Spielberger Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Social Adaptation Self-evaluation Scale (SASS). The patients with SAD also had higher scores on the future denial, threat prediction, self-denial, past denial, and interpersonal threat sections of the Depression and Anxiety Cognition Scale (DACS). NIRS scanning revealed hyperactivity in the left frontal cortex of patients with SAD. Threat prediction scores on DACS were negatively correlated with oxy-Hb responses in the right frontal cortex. LIMITATIONS: Further studies with a larger sample size are required to verify our findings. CONCLUSIONS: The results of this study demonstrate the different mechanisms of the right and left frontal cortex in situations of social anxiety disorder.

Genetic association of the transcription of neuroplasticity-related genes and variation in stress-coping style.

INTRODUCTION: Stress coping has been defined as the cognitive and behavioral efforts made to conquer, endure, or decrease external and internal demands and the conflicts between them. It has two main elements: the control or modification of the person-environment relationship causing the stress (i.e., problem-focused coping) and/or regulation of stressful feelings (i.e., emotion-focused coping). Research suggests that the expressions of brain-derived neurotrophic factor (BDNF) and neurotrophic tyrosine kinase receptor type 2 (NTRK2) play important roles in brain adaptation to investigate stress. To clarify the genetic basis of stress coping, we investigated the association of stress-coping strategies and social adaptation with single-nucleotide polymorphisms (SNPs) involved in neural plasticity, anxiety, and depression. METHODS: In 252 healthy controls (94 women; 158 men), we measured and estimated the stress-coping style using the Lazarus-type stress-coping inventory, ego aptitude scale (EAS), and social adaptation self-evaluation scale (SASS). We investigated one SNP of BDNF (rs6265, Val/Met) and five SNPs of NTRK2 (rs11140800, rs1187286, rs1867283, rs1147198, and rs10868235). RESULTS: We observed significant associations between BDNF and emotion-focused strategies, seeking social support, self-control, and distancing. We also found significant associations between NTRK2 and cognitive strategies, problem-solving, confrontive- coping, seeking social support, distancing and positive reappraisal. Significant associations were also found between BDNF and critical attitudes and between NTRK2 and all seven ego-related factors on the EAS. In the SASS, the minor allele rs1867283 of NTRK2 had a significantly higher score than the heterozygote. CONCLUSIONS: These findings may provide insights into the partial effects of genetic mutations in BDNF and NTRK2 on stress tolerance and personality.

Near-Infrared Spectroscopy during the Verbal Fluency Task before and after Treatment with Image Exposure and SSRI Therapy in Patients with Obsessive-Compulsive Disorder.

Drug therapy with selective serotonin reuptake inhibitors (SSRIs) has been used as a treatment for obsessive-compulsive disorder (OCD). In the present case report, exposure therapy was used in addition to escitalopram (20 mg) to treat a 28-year-old female patient with OCD for 6 months. Her obsessive-compulsive symptoms comprised thoughts of words such as rape, crematorium, neck hanging, unhappy, death, die, and kill and images such as a shelf of gods, a shrine, a Buddhist altar, the sun, the sky, and the faces of her parents, siblings, and relatives. As exposure therapy, she was asked to view the images associated with these symptoms three times a day along with drug therapy. With the combination of drug and exposure therapies, her obsessive-compulsive symptoms improved within 6 months, with no interference in her daily life. Multichannel near-infrared spectroscopy (NIRS) showed improvement of brain function in the temporal and frontal lobes after treatment. These results suggest that NIRS can be used as an indicator of brain function improvement in patients with OCD.

Rhenium-catalyzed regioselective synthesis of multisubstituted pyridines from ß-enamino ketones and alkynes via C-C bond cleavage.

A new method is described for the regioselective synthesis of multisubstituted pyridine derivatives. Treatment of N-acetyl ß-enamino ketones with alkynes in the presence of the rhenium catalyst, Re(2)(CO)(10), gives multisubstituted pyridines regioselectively. In this reaction, the N-acetyl moieties are important for the selective formation of the multisubstituted pyridines. This reaction proceeds via insertion of alkynes into a carbon-carbon single bond of ß-enamino ketones, intramolecular nucleophilic cyclization, and elimination of acetic acid.

Associations between baseline plasma MHPG (3-methoxy-4-hydroxyphenylglycol) levels and clinical responses with respect to milnacipran versus paroxetine treatment.

The purpose of this study was to investigate the effects of milnacipran and paroxetine on plasma levels of catecholamine metabolites, and we attempted to elucidate the differences between the mechanisms of these drugs in catecholaminergic neurons. In depressed patients, we investigated the relationships among pretreatment levels of catecholamine metabolites, the changes in plasma catecholamine metabolite levels before and after administration of milnacipran or paroxetine, and clinical response to these drugs. Responders to milnacipran showed lower pretreatment levels of plasma 3-methoxy-4-hydroxyphenylglycol (pMHPG) than did nonresponders to milnacipran; there was also a positive correlation between changes in pMHPG levels and percent improvement of the score on the 17-item Hamilton Rating Scale for Depression (HRSD). On the other hand, responders to paroxetine showed higher pretreatment levels of pMHPG than did nonresponders to paroxetine, and a negative correlation was observed between changes in pMHPG levels and percent improvement of the HRSD score. However, a significant difference was not observed in the pretreatment plasma level of homovanillic acid between responders and nonresponders to treatment with milnacipran or paroxetine. These results suggest that there is an association between baseline pMHPG levels and clinical responses with respect to milnacipran versus paroxetine treatment.