COVID-19 susceptibility and clinical outcomes in autoimmune inflammatory rheumatic diseases (AIRDs): a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to assess the susceptibility to and clinical outcomes of COVID-19 in autoimmune inflammatory rheumatic disease (AIRD) and following AIRD drug use. MATERIALS AND METHODS: We included observational and case-controlled studies assessing susceptibility and clinical outcomes of COVID-19 in patients with AIRD as well as the clinical outcomes of COVID-19 with or without use of steroids and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). RESULTS: Meta-analysis including three studies showed that patients with AIRD are not more susceptible to COVID-19 compared to patients without AIRD or the general population (OR: 1.11, 95% CI: 0.58 to 2.14). Incidence of severe outcomes of COVID-19 (OR: 1.34, 95% CI: 0.76 to 2.35) and COVID-19 related death (OR: 1.21, 95% CI: 0.68 to 2.16) also did not show significant difference. The clinical outcomes of COVID-19 among AIRD patients with and without csDMARD or steroid showed that both use of steroid (OR: 1.69, 95% CI: 0.96 to 2.98) or csDMARD (OR: 1.35, 95% CI: 0.63 to 3.08) had no effect on clinical outcomes of COVID-19. CONCLUSIONS: AIRD does not increase susceptibility to COVID-19, not affecting the clinical outcome of COVID-19. Similarly, the use of steroids or csDMARDs for AIRD does not worsen the clinical outcome.

Continuing perioperative estrogen therapy does not increase venous thromboembolic events in transgender patients: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to compare the risk of venous thromboembolic events (VTE) between patients suspending and continuing estrogen therapy perioperatively, in male to female gender-affirming surgery (vaginoplasty). MATERIALS AND METHODS: The authors conducted a systematic review and meta-analysis of existing research on male to female gender-affirming study, which compared the risk of VTE among the usage of estrogen perioperatively. RESULTS: A total of 209 studies were identified as potentially eligible among PubMed, Embase, and Cochrane library databases. Among the studies, 191 studies were excluded due to their abstract inappropriateness. Out of the remaining 18 studies, only 3 articles were eligible and were finally included. Meta-analysis was performed and showed odds ratio of 0.77 (95% CI: 0.04, 14.01). CONCLUSIONS: Perioperative estrogen therapy does not increase VTE risk on male to female gender-affirming surgery. Therefore, estrogen therapy may be continued perioperatively in vaginoplasty. More prospective studies are needed.

Periodontal Pathogens Modulate Lipid Flux via Fatty Acid Binding Protein 4.

A strong correlation between chronic periodontitis and systemic diseases (e.g., cardiovascular disease, metabolic disorders) has been suggested for several decades. However, the evidence supporting this correlation is restricted primarily to epidemiologic studies, with only a few experimental outcomes confirming such a correlation and providing information about the underlying molecular mechanisms. To reveal a correlation between periodontitis and systemic diseases as well as a relevant molecular pathway, we investigated the effects of Porphyromonas gingivalis and Fusobacterium nucleatum, which play roles in chronic periodontitis progression, on Raw264.7 and THP-1 macrophages. Infection with P. gingivalis or F. nucleatum significantly induced the expression of fatty acid binding protein 4 (FABP4), one of the most important adipokines that play a role in the progression of systemic diseases such as atherosclerosis and type 2 diabetes. Periodontal pathogen-induced FABP4 expression in macrophages promoted lipid uptake by these cells, as demonstrated by the diminished lipid accumulation in cells treated with an FABP4 inhibitor, BMS309403, or with knockdown of FABP4 expression. This periodontal pathogen-induced FABP4 expression was dependent on the JNK pathway, and JNK inhibition reduced lipid uptake by reducing FABP4 expression. Serum levels of antibodies against P. gingivalis correlated with serum FABP4 levels in humans, whereas no association occurred between F. nucleatum antibody titers and FABP4 levels. To our knowledge, this report is the first to experimentally demonstrate that periodontal pathogens stimulate lipid uptake in macrophages by modulating FABP4 expression. These findings strongly support the hypothesis that periodontitis may affect the progression of various systemic diseases.

Morphological Study of Poly(vinylbenzyl chloride)-Grafted Poly(ethylene-co-tetrafluoroethylene) [ETFE-g-PVBC] Films Using Small-Angle Neutron Scattering Analysis.

In this study, the effect of degree of the grafting and crosslinking on the morphology of the crystalline domain in poly(vinylbenzyl chloride)-grafted poly(ethylene-co-tetrafluoroethylene) [ETFE-g-PVBC] films was investigated using a SANS (small-angle neutron scattering) analysis. The grafted films can be used as a precursor for ion-exchange membrane. ETFE-g-PVBC films with various degrees of cross-linking were prepared by a simultaneous irradiation grafting of vinylbenzyl chloride (VBC) and divinylbenzene (DVB) onto an ETFE film. The SEM-EDX (scanning electron microscopy-energy dispersive X-ray spectroscopy) results of a cross-sectional distribution of ETFE-g-PVBC films showed that the chlorine atoms were well-distributed throughout the films. SANS profiles of the PVBC-grafted films in the absence of a DVB crosslinker showed that the crystalline domain peaks were observed and the peak maximum position shifted significantly from 0.032 Å-(-1) to 0.02 Å(-1) with an increase in the degree of grafting. However, peak maximum positions of the PVBC-grafted films in the presence of a DVB crosslinker shifted slightly from 0.02 Å(-1) to 0.024 Å(-1) with an increase in the amount of DVB monomer at same degree of grafting. These results indicate that the degree of grafting and crosslinking affect the morphology of the crystalline domain in the ETFE-g-PVBC films.

De novo DNA methylation of the paternal genome in 2-cell mouse embryos.

The developmental dynamics of DNA methylation events have been well studied. Active demethylation of the paternal genome occurs in the zygote, passive demethylation occurs during cleavage stages, and de novo methylation occurs by the blastocyst stage. It is believed that the paternal genome has lower levels of methylation during early development than the maternal genome. However, in this study, we provide direct and indirect evidence of genome-wide de novo DNA methylation of the paternal genome after the first cell cycle in mouse embryos. Although very little methylation was detected within the male pronucleus in zygotes, an intense methylation signal was clearly visible within the androgenetic 2-cell embryos. Moreover, the DNA methylation level of the paternal genome in the post-zygotic metaphase embryos was similar to that of the maternal genome. Using indirect immunofluorescence with an antibody to methylated lysine 9 in histone H3, we provided new evidence to support the concept of spatial compartmentalization of parental genomes in 2-cell mouse embryos. Nevertheless, the transient segregation of parental genomes was not observed by determining the DNA methylation distribution in the 2-cell embryos even though DNA methylation asymmetry between the maternal and paternal pronucleus existed in the 1-cell stage. The disappearance of separate immunofluorescence signals of 5-methyl cytosine in the 2-cell embryos might be attributed to the de novo methylation of the paternal genome during the first mitotic cycle.

Nizatidine improves clinical symptoms and gastric emptying in patients with functional dyspepsia accompanied by impaired gastric emptying.

BACKGROUND/AIMS: In this crossover study, we investigated whether nizatidine, a H(2)-receptor antagonist, can alleviate clinical symptoms and gastric emptying in patients with Rome III-based functional dyspepsia (FD) with or without impaired gastric emptying. METHODS: We enrolled 30 patients presenting with FD symptoms (epigastric pain syndrome, n = 6; postprandial distress syndrome, n = 24). Rome III-based FD patients were treated with nizatidine (300 mg/day) or placebo for 4 weeks in a crossover trial. Gastric motility was mainly evaluated with the T(max) value using the (13)C-acetate breath test. Meal-related symptoms were defined as postprandial fullness and early satiation. Gastroesophageal symptom was defined as a burning feeling rising from the stomach or lower chest up toward the neck. Acylated- and desacylated ghrelin levels were evaluated by the ELISA method. Clinical symptoms, gastric emptying and ghrelin levels were evaluated at three different points during the study (pretreatment, after 4 weeks former treatment and after 4 weeks later treatment). The primary end point of this study was to determine whether nizatidine would improve clinical symptoms and gastric emptying in FD patients with or without impaired gastric emptying via affecting ghrelin levels. RESULTS: Meal-related symptoms of the patients treated with nizatidine improved significantly (21/30; 70%) compared to those treated with placebo (3/30; 10%). In addition, nizatidine treatment also significantly improved gastroesophageal symptoms (16/30; 53%) compared to those treated with placebo (0/30; 0%). Nizatidine treatment in patients with FD accompanied by impaired gastric emptying significantly improved clinical symptoms and T(max) value as a marker of gastric emptying (10/11, 91%; 9/11, 82%) compared to placebo therapy, respectively. There were no significant differences in ghrelin levels between nizatidine treatment and placebo therapy. CONCLUSION: Nizatidine administration significantly improved both gastric emptying and clinical symptoms in FD patients with impaired gastric emptying.

Novel vaccines against influenza viruses.

Killed and live attenuated influenza virus vaccines are effective in preventing and curbing the spread of influenza epidemics when the strains present in the vaccines are closely matched with the predicted epidemic strains. These vaccines are primarily targeted to induce immunity to the variable major target antigen, hemagglutinin (HA) of influenza virus. However, current vaccines are not effective in preventing the emergence of new pandemic or highly virulent viruses. New approaches are being investigated to develop universal influenza virus vaccines as well as to apply more effective vaccine delivery methods. Conserved vaccine targets including the influenza M2 ion channel protein and HA stalk domains are being developed using recombinant technologies to improve the level of cross protection. In addition, recent studies provide evidence that vaccine supplements can provide avenues to further improve current vaccies.

The kinetics of photocatalytic degradation of aliphatic carboxylic acids in an UV/TiO2 suspension system.

Kinetic studies on the photocatalytic degradation of aliphatic carboxylic acids were carried out in a slurry photoreactor with in-situ monitoring, employing artificial UV light as the source of energy and nano-TiO2 powder as the catalyst. The influences on the photocatalytic degradation such as the initial concentration of reactant (C0), catalyst dosage (CTiO2), UV intensity (Ia) and pH value have been investigated. Good agreement has been obtained between the value calculated by Langmuir-Freundlich-Hinshelwood (L-F-H) model and experimental data, with coefficient of multiple determination (R2) varying from 0.880 to 0.999. The L-F-H model has been proven to be feasible in describing the kinetic characteristic of the photocatalytic degradation of aliphatic carboxylic acids. Moreover, the apparent reaction rate constant (k) of the photocatalytic degradation of dicarboxylic acids is higher than that of monocarboxylic acids with the same carbon atoms. This shows that the photocatalytic degradation rate is favoured by different chemical structure.

Factors associated with development of late significant tricuspid regurgitation after successful left-sided valve surgery.

BACKGROUND: Persistent significant tricuspid regurgitation (TR) after successful left-sided valve surgery is frequently reported. OBJECTIVES: To evaluate the incidence, risk factors and clinical impact of development of late significant TR after successful left-sided valve surgery. METHODS AND RESULTS: 638 patients (356 men, mean age 52 (SD 14) years) who had mild (or=3/4 at follow-up echocardiography. Clinical events were defined as cardiovascular death, repeated open-heart surgery, and congestive heart failure requiring hospital admission. The overall incidence of late significant TR was 7.7% (49/638). Age (hazard ratio (HR), 1.0, 95% CI, 1.0 to 1.1; p = 0.005), female gender (HR, 5.0; 95% CI 2.0 to 12.7; p = 0.001), rheumatic aetiology (HR, 3.8; 95% CI 1.4 to 10.3; p = 0.011), atrial fibrillation (Af) (HR, 2.6; 95% CI 1.1 to 6.4; p = 0.035) and peak pressure gradient of TR at follow-up (HR, 1.1; 95% CI 1.0 to 1.1; p<0.001) were independent factors associated with development of late significant TR. During clinical follow-up of 101 (24) months, patients who developed late significant TR showed a significantly lower 8-year clinical event-free survival rate (76 (6) vs 91 (1)%, p<0.001). CONCLUSIONS: Several clinical variables were independent risk factors for development of late significant TR. Early surgical intervention for TR in selected patients with these risk factors may be justified, even though they have only mild TR.

Three-dimensional characteristics of functional mitral regurgitation in patients with severe left ventricular dysfunction: a real-time three-dimensional colour Doppler echocardiography study.

OBJECTIVES: We sought to evaluate the three-dimensional (3D) features of functional mitral regurgitation (FMR) and their geometric determinants by real-time 3D colour Doppler echocardiography. METHODS: Real-time 3D colour Doppler echocardiography was performed in 52 patients with severe left ventricular dysfunction. With aliasing velocity set around 40 cm/s, proximal isovelocity surface area (PISA) radius was measured on medial, central and lateral antero-posterior planes at a mid-systole frame, and the largest (PISAmax) was determined. Geometric investigations of the left ventricle and mitral valve were performed. RESULTS: The distal length from the anterior leaflet angulation on the central plane was significantly longer in the 29 patients (56%) with eccentric PISA than in the 23 patients with central PISA (1.73 (0.44) vs 1.47 (0.33) cm, p<0.05). The 18 patients (35%) with both-sides dominant PISA had a smaller anterior leaflet bending angle (141 degrees (8 degrees ) vs 147 degrees (8 degrees ), p<0.05) and a longer distal length from the angulation on the central plane (1.80 (0.36) vs 1.51 (0.41) cm, p<0.05) than the remaining 34 patients. The 14 patients (27%) with separate PISAs had smaller PISAmax (0.33 (0.13) vs 0.45 (0.16) cm, p<0.05), and tenting height (0.91 (0.20) vs 1.06 (0.24) cm, p<0.05) and tenting area (2.1 (0.6) vs 2.7 (0.8) cm(2), p<0.05) on the central plane than in those with single PISA. CONCLUSIONS: 3D features of FMR are quite diverse. The shape and site of anterior leaflet bending determine the shape of the regurgitant orifice, and small mitral valve tenting generates separate small regurgitant orifices of FMR in patients with severe left ventricular dysfunction.

Quality of life outcomes following laparoscopic total mesorectal excision for low rectal cancers: a clinical control study.

AIMS: To evaluate the health-related quality of life (HRQoL) outcomes in patients undergoing laparoscopic total mesorectal excision (LTME) with anal sphincter preservation (ASP) for low rectal cancers. METHODS: Patients undergoing LTME with ASP or open procedures (OTME) for low rectal cancers were prospectively followed up. All patients were treated in curative attempt and were free of local recurrence during the study. HRQoL was assessed by questionnaires during 3-6 months, 12-18 months, and 2-5 years after surgery. RESULTS: From June 2001 to March 2006, 125 patients undergoing LTME and 103 undergoing OTME were included in this study. In contrast to OTME patients, the LTME ones showed significantly better physical function during 3-6 months after surgery, less micturition problems within 12-18 months, less male sexual problems and better sexual function during 12-18 months after surgery, with better sexual enjoyment after 24 months postoperatively. Both groups showed significant improvement in most subscales from the first to the second assessment, and an improvement in sexual enjoyment from the second to the third assessment. The sexual function, micturition problems and male sexual problems in the LTME group significantly improved from the first to the second assessment, whereas the sexual function in the OTME group improved from the second to the third assessment. CONCLUSIONS: Patients undergoing LTME for low rectal cancers can achieve superior postoperative HRQoL than patients undergoing OTME, with superior physical function, micturition function, overall sexual and male sexual functions in the short term, and better sexual enjoyment in the long term. The HRQoL of both LTME and OTME patients may be expected to improve over time, particularly over the first postoperative year.

Roles of NF-kappaB and bcl-2 in two differential modes of cell death of mouse cortical collecting duct cells.

Recent data have implicated nuclear factor-kappaB (NF-kappaB) and Bcl-2 in the regulation of apoptotic and necrotic cell death in various cells. However, mechanisms of their effects on cell death of renal epithelial cells are not clear. First, we investigated the effect of specific inhibition of NF-kappaB and overexpression of Bcl-2 on necrotic cell death induced by hydrogen peroxide or cisplatin in renal collecting duct cells. M-1 cells, which were derived from outer cortical collecting duct, were stably transfected with the non-phosphorylatable mutant of inhibitory-kappaBalpha (I-kappaBalpha) and Bcl-2. Overexpression of I-kappaBalpha and Bcl-2 did not affect cisplatin-induced necrotic cell death, but overexpression of I-kappaBalpha significantly decreased H2O2-induced cell death. Regarding apoptotic cell death induced by cisplatin, serum deprivation and contact inhibition was increased by overexpression of I-kappaBalpha, whereas overexpression of bcl-2 inhibited the apoptotic cell death. I-kappaBalpha overexpression increased Bax expression and decreased cIAP-1 and -2 expression compared to vector-transfected cells, but did not alter SAPK/JNK activity in the presence or absence of cisplatin. NF-kappaB activity was significantly higher in bcl-2-overexpressing cells than in control cells. These data show that activation of NF-kappaB mediates H2O2-induced necrotic injury, but inhibits apoptotic cell death in renal collecting duct cells, and that Bcl-2 selectively protects apoptotic cell death in M-1 cells.

Development of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo diagnosis.

In this work, the development and applications of a fluorescence detection system using optical parametric oscillator (OPO) laser excitation for in vivo disease diagnosis including oral carcinoma are described. The optical diagnosis system was based on an OPO laser for multi-wavelength excitation and time-resolved detection. The pulsed Nd-YAG-pumped OPO laser system (6 ns, 20 Hz) is compact and has a rapid, broad, and uniform tuning range. Time-gated detection of intensified charge-coupled device (ICCD) making use of external triggering was used to effectively eliminate the laser scattering and contribute to the highly sensitive in vivo measurements. Artificial tissue-simulating phantoms consisting of polystyrene microspheres and tissue fluorophores were tested to optimize the gating parameters. 51-ns gate width and 39-ns gate delays were determined to be the optimal parameters for sensitive detection. In vivo measurements with the optical diagnosis system were applied to esophagus, stomach, and small intestine using an endoscope in canine animal studies. The rapid tuning capability of the optical diagnosis system contributed greatly to the optimization of wavelength for the observation of porphyrin in the small intestine. When the small intestine was thoroughly washed with water, the emission band which corresponds to porphyrin disappeared. Based on this observation, it was concluded that the detected signal was yielded by porphyrin-containing bile secretion. Also, multispectral analyses using multiple excitations from 415 to 480 nm at 5 nm intervals confirmed the porphyrin detection in the small intestine. The optical diagnosis system was also applied to the detection of human xenograft of oral carcinoma in mice using 5-aminolevulinic acid (5-ALA) which is a photodynamic therapy (PDT) drug. Significant differences in protoporphyrin IX fluorescence intensity between normal and tumor tissue could be obtained 2 hours after the injection of 5-ALA into mice due to the preferential accumulation of 5-ALA in tumors. Results reported herein demonstrate potential capabilities of the LIF-OPO system for in vivo disease diagnosis.