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Lactoferrin (LF) is a multifunctional glycoprotein in mammalian milk. In a previous report, we showed that enteric-coated bovine LF tablets can decrease visceral fat accumulation, hypothesising that the enteric coating is critical to the functional peptides reaching the visceral fat tissue and exerting their anti-adipogenic activity. The aim of the present study was to assess whether ingested LF can retain its anti-adipogenic activity. We therefore investigated the effects of LF and LF treated with digestive enzymes (the stomach enzyme pepsin and the small intestine enzyme trypsin) on lipid accumulation in pre-adipocytes derived from the mesenteric fat tissue of male Sprague–Dawley rats. Lipid accumulation in pre-adipocytes was significantly reduced by LF in a dose-dependent manner and was associated with reduction in gene expression of CCAAT/enhancer binding protein delta, CCAAT/enhancer binding protein alpha and PPARγ as revealed by DNA microarray analysis. Trypsin-treated LF continued to show anti-adipogenic action, whereas pepsin-treated LF abrogated the activity. When an LF solution (1000 mg bovine LF) was administered by gastric intubation to Sprague–Dawley rats, immunoreactive LF determined by ELISA could be detected in mesenteric fat tissue at a concentration of 14·4 μg/g fat after 15 min. The overall results point to the importance of enteric coating for action of LF as a visceral fat-reducing agent when administered in oral form.

Lactoferrin (LF), a multifunctional glycoprotein in mammalian milk, is reported to exert a modulatory effect on lipid metabolism. The aim of the present study was to elucidate whether enteric-coated LF (eLF) might improve visceral fat-type obesity, an underlying cause of the metabolic syndrome. Using a double-blind, placebo-controlled design, Japanese men and women (n 26; aged 22–60 years) with abdominal obesity (BMI>25 kg/m2, and visceral fat area (VFA)>100 cm2) consumed eLF (300 mg/d as bovine LF) or placebo tablets for 8 weeks. Measurement of the total fat area, VFA and subcutaneous fat area from computed tomography images revealed a significant reduction in VFA ( − 14·6 cm2) in the eLF group, as compared with the placebo controls ( − 1·8 cm2; P = 0·009 by ANCOVA). Decreases in body weight, BMI and hip circumference in the eLF group ( − 1·5 kg, − 0·6 kg/m2, − 2·6 cm) were also found to be significantly greater than with the placebo (+1·0 kg, +0·3 kg/m2, − 0·2 cm; P = 0·032, 0·013, 0·041, respectively). There was also a tendency for a reduction in waist circumference in the eLF group ( − 4·4 cm) as compared with the placebo group ( − 0·9 cm; P = 0·073). No adverse effects of the eLF treatment were found with regard to blood lipid or biochemical parameters. From these results, eLF appears to be a promising agent for the control of visceral fat accumulation.

The prevalence of the Omicron subvariant BA.2.75 rapidly increased in India and Nepal during the summer of 2022, and spread globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs is higher than that of BA.2 and BA.5. Of note, BA.2.75 causes focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which is not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicates better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 in a hamster model and should be closely monitored. Omicron subvariants may differ in their replicative fitness and their potential to cause more severe disease. In this study, the authors characterized Omicron BA.2.75 in a hamster model and found that it replicates more efficiently in the lungs than BA.2 and BA.5.

Background Although antidepressant monotherapy is recommended for patients with major depressive disorder (MDD), they often do not respond to it, necessitating alternatives such as electroconvulsive therapy (ECT). However, maintenance pharmacotherapy after ECT has remained unestablished. This study, conducted at 240 facilities throughout Japan, aimed to explore maintenance pharmacotherapy after ECT for 3,749 inpatients with MDD. Methods The patients were divided into two groups, one that underwent ECT (ECT group, N  = 521) and another that did not (non-ECT group, N  = 3,273), for the comparison of clinical characteristics and prescription details at discharge. The primary outcome of this study was the prescription rate of antidepressant monotherapy at discharge, while the secondary outcomes included prescription rates of specific combination regimens, such as antidepressant plus lithium. Results We identified 198 prescription patterns involving antidepressants in the ECT group. Analysis by drug category revealed distinctive patterns: there was no statistically significant difference in prescription rates for antidepressant monotherapy between the ECT and non-ECT groups ( N  = 118, 22.6% vs. N  = 932, 28.4%). In contrast, the prescription rate for the combination of antidepressant and antipsychotic medications was significantly higher in the ECT group ( N  = 188, 36.0% vs. N  = 941, 28.7%). The combination of antidepressant and mood stabilizer was also more frequent in the ECT group ( N  = 35, 6.7% vs. N  = 130, 3.9%), although this difference did not reach statistical significance after Bonferroni correction. At the drug level, additional distinctive patterns emerged: among antidepressant monotherapies, nortriptyline use was significantly more common in the ECT group ( N  = 9, 1.7% vs. N  = 11, 0.3%). For mood stabilizers, restricting the analysis to lithium revealed a markedly higher rate in the ECT group ( N  = 30, 5.7% vs. N  = 35, 1.0%). Conclusions These findings highlight the complexity of treatment decisions managing of MDD after ECT and emphasize the need for structured prospective research on the effectiveness of specific maintenance pharmacotherapies after ECT.

A high-flow nasal cannula (HFNC) therapy plays a significant role in providing respiratory support to critically ill patients with coronavirus disease 2019 (COVID-19); however, the dispersion of the virus owing to aerosol generation is a matter of concern. This study aimed to evaluate if HFNC disperses the virus into the air. Among patients with COVID-19 admitted to private rooms with controlled negative pressure, we enrolled those admitted within 10 days of onset and requiring oxygenation through a conventional nasal cannula or HFNC therapy. Of the 17 patients enrolled, we obtained 22 samples (11 in the conventional nasal cannula group and 11 in the HFNC group). Viral RNA was detected in 20 nasopharyngeal swabs, and viable viruses were isolated from three nasopharyngeal swabs. Neither viral RNA nor viable virus was detected in the air sample at 0.5 m regardless of the oxygen-supplementation device. We detected viral RNA in two samples in the conventional nasal cannula group but not in the HFNC therapy group in gelatin filters located 3 m from the patient and the surface of the ventilation. This study directly demonstrated that despite viral RNA detection in the nasopharynx, viruses may not be dispersed by HFNC therapy. This warrants further research to determine if similar results can be obtained under different conditions.

The influence of polyvascular disease (PVD) on the short- and long-term clinical outcomes of patients undergoing transcatheter aortic valve implantation via trans-femoral access (TF-TAVI) has not been fully elucidated. A total of 2167 patients from the Optimized CathEter vAlvular iNtervention-TAVI (OCEAN-TAVI) registry who underwent TF-TAVI was studied. PVD was defined as the presence of at least two of the following vascular bed (VB) diseases: concomitant coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral artery disease (PAD). Patients with PVD (288 patients, 13.3%) had a higher incidence of in-hospital complications, such as AKI (16.3% vs. 7.0%, p<0.01) and disabling stroke (3.5% vs. 1.2%, p<0.01) than patients without PVD. These complications caused higher rates of procedural mortality (4.5% vs. 2.0%, p<0.01). PVD increased the risk of the 2-year rate of cardiovascular death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.04-2.50; p<0.05); however, non-cardiovascular death, myocardial infarction, or ischemic stroke was not associated with PVD. Worsening heart failure (4.6% vs. 1.1%, p<0.01) was the main cause of cardiovascular death among patients with PVD. In a sub-analysis, compared with patients with AS alone, those with 2 VB diseases (CAD+PAD; adjusted HR, 1.93; 95% CI, 1.06-3.53; p<0.05) and 3 VB diseases (CAD+CVD+PAD; adjusted HR, 2.61; 95% CI, 1.21-5.62; p<0.05) had a higher risk of 2-year cardiovascular death. The increased prevalence of concomitant atherosclerotic VB diseases before TF-TAVI may increase the rates of in-hospital complications and 2-year cardiovascular death. Given the higher rate of mortality in patients with PVD undergoing TF-TAVI, future studies focusing on medical therapy are needed to reduce long-term cardiovascular events in this high-risk subset.

Keratinocytes in the oral mucosal epithelium, which is a non-keratinized stratified epithelium, are exposed to various stimuli from the oral cavity. JNK and p38 are stress-activated mitogen-activated protein kinases (MAPKs) that are phosphorylated by various stimuli and are involved in the assembly and disassembly of tight junctions (TJs) in keratinocytes. Therefore, we investigated the effects of stress-activated MAPKs on TJs in a mouse keratinocyte cell line during cell–cell junction formation in two-dimensional (2D) cultures or stratification to form non-keratinized epithelium in 3D cultures. In 2D cultures, calcium induced zipper-like staining for ZO-1 at 2 h and string-like staining for ZO-1 at 12 h, which indicated immature and mature cell–cell junctions, respectively. Anisomycin (AM), a JNK and p38 activator, inhibited formation of string-like staining for ZO-1, whereas inhibition of JNK, but not p38, after AM treatment restored string-like staining for ZO-1, although claudins (CLDNs) 4, 6, and 7 did not completely colocalize to ZO-1-positive sites. In 3D cultures, AM treatment for 2 weeks activated only p38, suppressed flattening of the superficial cells, removed CLDN7 from ZO-1-positive spots on the surface of 3D cultures, which represent TJs, and decreased transepithelial electrical resistance. Thus, short-term AM treatment inhibited maturation of cell–cell junctions by JNK, but not p38, activation. p38 activation by long-term AM treatment affected morphology of stratified structures and paracellular permeability, which was increased by CLDN7 removal from TJs. Various chronic stimuli that activate stress-activated MAPKs may weaken the keratinocyte barrier and be involved in TJ-related diseases.

Background The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment‐resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine. Methods After attending a 1‐day educational program on schizophrenia based on the \"Guidelines for the Pharmacological Treatment of Schizophrenia,\" we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty‐nine facilities in 2017 were included in the study. Results There were dichotomous distributions in the examination rate of TRS and a non‐normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (r s = 0.531, P = 1.032 × 10−4). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS. Conclusion As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families. A significant difference was found (P = .041) in the prescription rate of clozapine between the three groups according to the examination rate of TRS. Post hoc analysis revealed that the prescription rate of clozapine in facilities with a high examination rate (P = .014) was significantly higher than that in facilities with a low examination rate of TRS.