First Observation of the ß3αp Decay of

The ß-delayed proton decay of ^{13}O has previously been studied, but the direct observation of ß-delayed 3αp decay has not been reported. Rare 3αp events from the decay of excited states in ^{13}N^{⋆} provide a sensitive probe of cluster configurations in ^{13}N. To measure the low-energy products following ß-delayed 3αp decay, the Texas Active Target (TexAT) time projection chamber was employed using the one-at-a-time ß-delayed charged-particle spectroscopy technique at the Cyclotron Institute, Texas A&M University. A total of 1.9×10^{5} ^{13}O implantations were made inside the TexAT time projection chamber. A total of 149 3αp events were observed, yielding a ß-delayed 3αp branching ratio of 0.078(6)%. Four previously unknown α-decaying excited states were observed in ^{13}N at 11.3, 12.4, 13.1, and 13.7 MeV decaying via the 3α+p channel.

Clinical characteristics and associated factors of qualitative olfactory dysfunction.

BACKGROUND: Although interest in qualitative olfactory dysfunction (OD), including parosmia and phantosmia, has been increasing since the COVID-19 pandemic, little is known about the clinical characteristics and associated factors of qualitative OD. METHODS: Adult patients with subjective smell disturbance who underwent both the olfactory questionnaire and psychophysical olfactory function test were retrospectively enrolled. Demographic and clinical characteristics were analysed according to the presence or absence of parosmia or phantosmia. RESULTS: Among a total of 753 patients with self-reported OD, 60 (8%) and 167 (22.2%) patients reported parosmia and phantosmia, respectively. Younger age and female sex were related to both parosmia and phantosmia. The frequency of parosmia was significantly higher in patients with post-viral OD (17.9%) than in patients with the sinonasal disease (5.5%), whereas that of phantosmia was not different according to aetiologies of OD. Patients with COVID-19 had significantly younger ages and higher TDI scores than those with other viral infections. Remarkably, patients with parosmia or phantosmia had significantly higher TDI scores than those without but experienced more disruption in daily life. In the multivariate analysis, younger age and higher TDI score were identified as independent factors associated with both parosmia and phantosmia, while the viral infection was associated with parosmia but not with phantosmia. CONCLUSIONS: Patients with OD who have parosmia or phantosmia have higher odour sensitivity than those who do not, but experience more deterioration in the quality of life. Viral infection is a risk factor for parosmia but not for phantosmia.

Incidence of idiopathic benign paroxysmal positional vertigo subtype by hospital visit type: experience of a single tertiary referral centre.

OBJECTIVE: To investigate the incidence of benign paroxysmal positional vertigo subtype by hospital visit type (i.e. out-patient department vs emergency room), in a single tertiary referral centre. METHODS: A total of 772 consecutive patients with benign paroxysmal positional vertigo were included. Using head-roll and Dix-Hallpike tests, benign paroxysmal positional vertigo subtype was determined as canalolithiasis posterior semicircular canal benign paroxysmal positional vertigo, geotropic horizontal semicircular canal benign paroxysmal positional vertigo or apogeotropic benign paroxysmal positional vertigo. RESULTS: The posterior semicircular canal benign paroxysmal positional vertigo patients who were evaluated via the out-patient department outnumbered those evaluated via the emergency room, while those with horizontal semicircular canal benign paroxysmal positional vertigo who were evaluated via the emergency room outnumbered those evaluated via the out-patient department. CONCLUSION: A significantly higher proportion of patients who visited the emergency room had horizontal semicircular canal benign paroxysmal positional vertigo than posterior semicircular canal benign paroxysmal positional vertigo. These results suggest that the true incidence of horizontal semicircular canal benign paroxysmal positional vertigo might be higher than previously reported.

Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.

BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO. AIM: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage. METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube. FINDINGS: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT. CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.

Gustatory dysfunction in patients with olfactory dysfunction and the associated factors.

BACKGROUND: Little is known about the occurrence of gustatory dysfunction (GD) in relation to different aetiologies of olfactory dysfunction (OD) as assessed by psychophysical chemosensory tests. The aim of this study was to analyse gustatory function in patients with OD and to investigate clinical factors associated with GD. METHODS: A total of 742 individuals who underwent both olfactory and gustatory function tests at a tertiary medical centre from November 2019 to March 2021 were retrospectively enrolled. Olfactory and gustatory function were assessed by the YSK olfactory and gustatory function tests, respectively. Patients with OD were classified into four groups according to the aetiology: sinonasal disease, post-infection OD (PIOD), post-traumatic OD (PTOD), and others. Secondary outcomes included age, sex, smoking history, and alcohol history. RESULTS: Among the 488 patients with OD, 93 (19.1%) showed GD and 395 (80.9%) had normal gustatory function. Only 25 (9.8%) among 254 individuals with normosmia showed GD. Analyses of these frequencies revealed a significant association between OD and GD. In addition, the taste score was significantly lower in patients with OD than individuals with normosmia. The frequency of GD was significantly higher in patients with PTOD (53.6%) than in those with OD of other aetiologies (sinonasal disease, 6.7%; PIOD, 13.0%; others, 24.4%). In the multivariate analysis, age >=5 years and PTOD were associated with a high frequency of GD among patients with OD. CONCLUSIONS: The current study show that GD is significantly associated with OD. In particular, GD is more common in patients with PTOD than in those with OD of other aetiologies.

Association between the use of electronic cigarettes and the prevalence of chronic rhinosinusitis and allergic rhinitis: a nationwide cross-sectional study.

BACKGROUND: Whether the use of electronic cigarettes (ECs) is associated with upper airway diseases, including chronic rhinosinusitis (CRS) and allergic rhinitis (AR), remains unclear. METHODS: We analyzed data from the nationwide cross-sectional surveys: the Korea National Health and Nutrition Examination Survey VI (2013-2015), VII (2016-2018), and VIII (2019). Logistic regression analysis was performed to assess the association between EC use and CRS or AR. RESULTS: Among a total of 38,413 participants, 6.4% were former EC users and 2.5% were current EC users. Former EC users and current EC showed a significantly increased OR for CRS or AR compared with never EC users. In the subgroup analysis, the "current CC (conventional cigarette)-current EC" and the "current CC-formal EC" group had a significantly higher OR for CRS or AR than the "current CC-never EC" group. In addition, former CC smokers who currently use ECs showed a significantly higher OR for AR than former CC smokers without EC use. CONCLUSIONS: EC use is significantly associated with a high prevalence of CRS and AR in the adult population. These results indicate that the use of ECs may increase the risk of upper airway disease.

Association of the human papillomavirus infection with the recurrence of sinonasal inverted papilloma: a systematic review and meta-analysis.

BACKGROUND: Although the role of human papillomavirus (HPV) in sinonasal inverted papilloma (SNIP) has been investigated, the link between HPV infection and SNIP recurrence remains controversial. This meta-analysis aimed to investigate the association between HPV infection and recurrence of SNIP. METHODS: The PubMed, Web of Science, Google Scholar, and Cochrane Library databases were searched (until 16 June 2021) to collect all relevant articles. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using the fixed effects model. In addition, subgroup analysis, assessment of publication bias, and sensitivity analyses were performed. RESULTS: Fourteen eligible articles, including 592 patients with SNIP, were included in this study. Pooled analysis revealed that HPV-positive cases exhibited a significantly higher OR of tumour recurrence than HPV-negative counterparts). A significant association between HPV infection and tumour recurrence remained stable in subgroup analyses according to the publication year of the studies. CONCLUSIONS: Our meta-analysis demonstrates that HPV infection is significantly associated with the recurrence of SNIP, suggesting the pathological role of HPV in SNIP. These results suggest that HPV infection should be considered in the management of SNIP.

Differences and similarities between the upper and lower airway: focusing on innate immunity.

The nose is the first respiratory barrier to external pathogens, allergens, pollutants, or cigarette smoke, and vigorous immune responses are triggered when external pathogens come in contact with the nasal epithelium. The mucosal epithelial cells of the nose are essential to the innate immune response against external pathogens and transmit signals that modulate the adaptive immune response. The upper and lower airways share many physiological and immunological features, but there are also numerous differences. It is crucial to understand these differences and their contribution to pathophysiology in order to optimize treatments for inflammatory diseases of the respiratory tract. This review summarizes important differences in the embryological development, histological features, microbiota, immune responses, and cellular subtypes of mucosal epithelial cells of the nose and lungs.

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis.

BACKGROUND AND PURPOSE: The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA. MATERIALS AND METHODS: Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0-2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders. RESULTS: Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20-4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02-2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04-1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 -6.12; P = .099). CONCLUSIONS: Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Compressive stress induces collective migration through cytoskeletal remodelling in nasal polyp epithelium.

BACKGROUND: Nasal polyps in the nasal cavity and mucous discharge inside the maxillary sinus exhibit compressive stress on the nasal mucosal epithelium. However, there have been only a few studies on how compressive stress impacts the human nasal mucosal epithelium. METHODOLOGY: We investigated the effect of compressive stress on collective migration, junctional proteins, transepithelial electri- cal resistance, epithelial permeability, and gene expression in well-differentiated normal human nasal epithelial (NHNE) cells and human nasal polyp epithelial (HNPE) cells. RESULTS: NHNE cells barely showed collective migration at compressive stress up to 150 mmH20. However, HNPE cells showed much greater degree of collective migration at a lower compressive stress of 100 mmH20. The cell migration of HNPE cells sub- jected to 100 mmH2O compression was significantly decreased at day 3 and was recovered to the status prior to the compressive stress by day 7, indicating that HNPE cells are relatively more sensitive to mechanical pressure than NHNE cells. Compressive stress also increased transepithelial electrical resistance and decreased epithelial permeability, indicating that the compressive stress disturbed the structural organization rather than physical interactions between cells. In addition, we found that compressive stress induced gene expressions relevant to airway inflammation and tissue remodelling in HNPE cells. CONCLUSION: Taken together, these findings demonstrate that compressive stress on nasal polyp epithelium is capable of inducing collective migration and induce increased expression of genes related to airway inflammation, innate immunity, and polyp remo- delling, even in the absence of inflammatory mediators.

Alterations in central hemodynamic in patients with COPD after acute high intensity exercise.

The present study investigated the relationship between central hemodynamics and lung function and the response to an acute bout of exercise in COPD. METHODS: Based on the severity of COPD, moderate group (MOD, n = 12) and more mild group (MLD, n = 12) underwent central hemodynamic assessments pre- and post-peak exercise. RESULTS: In the entire cohort (n = 24), central diastolic blood pressure (cDBP) was associated with pulmonary function. Post-exercise, cDBP remained elevated (p < 0.01), however, peripheral diastolic blood pressure (pDBP) was reduced (p = 0.02). Prior to exercise, the MOD showed higher cDBP and heart rate (HR) than the MLD (p = 0.02 and p = 0.01, respectively), but no difference in central aortic/arterial stiffness (p > 0.05). These findings remained similar post-exercise. CONCLUSION: Central diastolic blood pressure is linked to pulmonary function in COPD and it is elevated after exercise-induced reductions in pDBP. Central diastolic blood pressure is higher in the MOD than the MLD, however, there was no difference in central aortic/arterial stiffness between groups.

A ligand-independent fast function of RARα promotes exit from metabolic quiescence upon T cell activation and controls T cell differentiation.

Vitamin A metabolites play important roles in T cell activation and differentiation. A conventional model of RARα function relies upon retinoic acid (RA)-liganded RARα binding to specific DNA motifs to regulate gene expression in the nucleus. However, this genomic function fails to explain many of the biological responses of the RA-RARα axis on T cells. We generated a mouse line where RARα is over-expressed in T cells to probe RARα function with unprecedented sensitivity. Using this model together with mice specifically lacking RARα in T cells, we found that RARα is required for prompt exit from metabolic quiescence in resting T cells upon T cell activation. The positive effect of RARα on metabolism is mediated through PI3K and subsequent activation of the Akt and mTOR signaling pathway. This largely non-genomic function of RARα is surprisingly ligand-independent and controls the differentiation of effector and regulatory T cell subsets.

The effects of hidden female smokers on the association between smoking and chronic obstructive pulmonary disease in Korean adults.

OBJECTIVE: Smoking is an important causative factor of chronic obstructive pulmonary disease (COPD), and females are considered more susceptible to the effects of smoking than males. However, in previous Korean studies, the effects of sex differences on the association between smoking and COPD have been controversial. In this study, the effects of sex differences on the association between smoking and COPD and the effects of female hidden smokers on that association in Korean adults were investigated. METHODS: Data were acquired from the Korea National Health and Nutrition Examination Surveys (KNHANES). RESULTS: The multivariate logistic regression analysis showed that self-reported smoking status for ex-smoker and current smoker correlated with COPD (odds ratio, OR: 1.67 and OR: 2.41, respectively). Self-reported smoking status for ex-smoker and current smoker correlated with COPD in men (OR: 1.61, OR: 2.43, respectively). Female self-reported current smoking status correlated with COPD (OR: 2.52), but female ex-smoker status was not significantly correlated with COPD. The ratios of cotinine-verified to self-reported smoking rates were 1.95 for women and 1.07 for men. CONCLUSION: The results of this study were that sex differences might affect the association between COPD and smoking and that female hidden smoking might affect the association between smoking and COPD in Korean adults.

Uremic solutes of indoxyl sulfate and p-cresol enhance protease-activated receptor-2 expression in vitro and in vivo in keratinocytes.

OBJECTIVES: Uremic pruritus is common in patients with chronic kidney disease (CKD). The retention of uremic solutes is thought to be associated with uremic pruritus. Meanwhile, activation of protease-activated receptor-2 (PAR-2) has been suggested to play an important role in pruritus. The present study was performed to investigate the effects of uremic solutes on the expression of PAR-2 in the skin. METHODS: Indoxyl sulfate (IS), p-cresol (PC), and uremic sera from CKD patients were used to stimulate PAR-2 expression in normal human epidermal keratinocytes (NHEKs). Also, NHEKs were additionally pretreated with soybean trypsin inhibitor to evaluate its inhibitory effect on PAR-2 expression. Patterns of cutaneous PAR-2 expression were investigated in skin samples from five CKD patients and CKD mice. RESULTS: In NHEKs, IS, PC, and sera from CKD patients significantly induced PAR-2 mRNA and protein expression. Soybean trypsin inhibitor significantly decreased PAR-2 mRNA and protein expression in NHEKs treated with IS, PC, and CKD sera. NHEKs treated with IS and PC exhibited significant increases in protease activity. Skin from both CKD patients and mice exhibited marked upregulation of PAR-2 expression compared to control skin. CONCLUSIONS: Results from the present study suggest that uremic solutes either directly or indirectly affect PAR-2 expression in the skin of CKD subjects, potentially playing an important role in the pathogenesis of uremic pruritus.

High-mobility group box 1 protein induces epithelialmesenchymal transition in upper airway epithelial cells.

BACKGROUND: In the treatment of rhinosinusitis, nasal polyps are a major problem, and the epithelial-to-mesenchymal transition (EMT) process is considered pivotal in their development. Although various studies have addressed the role of high mobility group box 1 (HMGB1) nuclear protein in this setting, its impact on EMT has yet to be evaluated. Our aim was the pathogenic mechanism of HMGB1 in EMT and EMT-induced upper respiratory nasal polyps. METHODS: We investigated the EMT-related effects of HMGB1 in human nasal epithelial (HNE) cells using western blot analysis, transepithelial-electrical resistance (TEER) testing, wound healing assay, and immunofluorescence. HNE cells were incubated in a low-oxygen environment to evaluate the role of HMGB1 in hypoxia-induced EMT. Further support for our in vitro findings was obtained through murine models. Human nasal polyps and nasal lavage fluid samples were collected for western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: HMGB1 increased mesenchymal markers and decreased epithelial markers in HNE cells. Hypoxia-induced HMGB1 in turn induced EMT, apparently through RAGE signaling. We verified HMGB1-induced EMT in the upper respiratory epithelium of mice by instilling intranasal HMGB1. In testing of human nasal polyps, HMGB1 and mesenchymal markers were heightened, whereas epithelial markers were reduced, compared with tissue controls. CONCLUSION: HMGB1 secretion in nasal epithelium may be a major pathogenic factor in upper respiratory EMT, contributing to nasal polyps.

[Melatonin Induces Apoptotic Cell Death in 3T3-L1 Preadipocytes].

Obesity is a major disease that causes significant complications. Inhibition of preadipocyte proliferation has the potential to prevent obesity and metabolic diseases. Melatonin is a pineal gland hormone that has various effects on cells and tissues. In this research, we investigated whether melatonin induces apoptosis in 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were cultured until confluence and then treated with 0, 10, 100, and 1000 µM melatonin for 1, 3, and 5 days. A cell viability assay kit was used for determining cell viability. Cell death marker proteins were assessed by Western blot analysis using GAPDH for control. Apoptotic morphological changes with nuclei fragmentation were observed using DAPI staining. Melatonin treatment decreased the phosphorylated extracellular signal-regulated kinases (p-ERK) activation while increasing the activation of caspase-3, 8, and 9. Furthermore, melatonin not only increased Bcl-2-associated X protein (Bax) but decreased B-cell lymphoma 2 (Bcl-2) expression as dose increases from 0 to 1000 µM. The melatonin treatment also suppressed the growth of preadipocytes with increasing concentration. These effects were attenuated by luzindole, a melatonin receptor antagonist and U0126, an inhibitor of p-ERK activation. In conclusion, melatonin can induce apoptosis of 3T3-L1 preadipocytes via p-ERK decrease.

A new aortoiliac calcification scoring system to predict grade C anastomotic leak following rectal cancer surgery.

BACKGROUND: Aortoiliac calcification may be a surrogate marker of decreased visceral perfusion causing anastomotic leak (AL). The aim of this study was to evaluate the predictive role of aortoiliac calcification for AL after rectal cancer surgery. METHODS: We enrolled patients with primary rectal cancer who had restorative resection at our institution between January 2013 and December 2015. An aortoiliac calcification score was calculated as the sum of calcification scores at the infrarenal aorta (0: no, 1: ≤ 3 cm, 2: > 3 cm) and the common iliac arteries (0: no, 1: unilateral, 2: bilateral). AL was classified into three grades: grade A, requiring no intervention; grade B, requiring therapeutic intervention without re-laparotomy; and grade C, requiring re-laparotomy. Clinicopathological characteristics were analyzed to identify risk factors for AL. RESULTS: There were 583 patients. Three-hundred forty-five (59.2%) had an aortoiliac calcification score ≥ 3, and 37 (6.3%) patients experienced AL, in 30 cases (5.1%) grade C AL. Patients with an aortoiliac calcification score ≥ 3 had a higher incidence of grade C AL (6.7% vs. 2.9%, p = 0.045). Multivariate logistic regression analysis revealed that an aortoiliac calcification score ≥ 3 was an independent risk factor for grade C AL (odds ratio = 2.669, 95% confidence interval 1.066-6.686, p = 0.036). CONCLUSIONS: Aortoiliac calcification may be considered a risk factor for grade C AL after rectal cancer surgery.