The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

Antibiotics versus placebo for acute bacterial conjunctivitis.

BACKGROUND: Acute bacterial conjunctivitis is an infection of the conjunctiva and is one of the most common ocular disorders in primary care. Antibiotics are generally prescribed on the basis that they may speed recovery, reduce persistence, and prevent keratitis. However, many cases of acute bacterial conjunctivitis are self-limited, resolving without antibiotic therapy. This Cochrane Review was first published in The Cochrane Library in 1999, then updated in 2006, 2012, and 2022. OBJECTIVES: To assess the benefits and side effects of antibiotic therapy in the management of acute bacterial conjunctivitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2022, Issue 5), MEDLINE (January 1950 to May 2022), Embase (January 1980 to May 2022), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www. CLINICALTRIALS: gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases in May 2022.   SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which any form of antibiotic treatment, with or without steroid, had been compared with placebo/vehicle in the management of acute bacterial conjunctivitis. This included topical and systemic antibiotic treatments. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the titles and abstracts of identified studies. We assessed the full text of all potentially relevant studies and determined the included RCTs, which were further assessed for risk of bias using Cochrane methodology. We performed data extraction in a standardized manner and conducted random-effects meta-analyses using RevMan Web. MAIN RESULTS: We included 21 eligible RCTs, 10 of which were newly identified in this update. A total of 8805 participants were randomized. All treatments were topical in the form of drops or ointment. The trials were heterogeneous in terms of their eligibility criteria, the nature of the intervention (antibiotic drug class, which included fluoroquinolones [FQs] and non-FQs; dosage frequency; duration of treatment), the outcomes assessed and the time points of assessment. We judged one trial to be of high risk of bias, four as low risk of bias, and the others as raising some concerns. Based on intention-to-treat (ITT) population, antibiotics likely improved clinical cure (resolution of clinical symptoms or signs) by 26% (RR 1.26, 95% CI 1.09 to 1.46; 5 trials, 1474 participants; moderate certainty) as compared with placebo. Subgroup analysis showed no differences by antibiotic class (P = 0.67) or treatment duration (P = 0.60). In the placebo group, 55.5% (408/735) of participants had spontaneous clinical resolution by days 4 to 9 versus 68.2% (504/739) of participants treated with an antibiotic. Based on modified ITT population, in which participants were analyzed after randomization on the basis of positive microbiological culture, antibiotics likely increased microbiological cure (RR 1.53, 95% CI 1.34 to 1.74; 10 trials, 2827 participants) compared with placebo at the end of therapy; there were no subgroup differences by drug class (P = 0.60). No study evaluated the cost-effectiveness of antibiotic treatment. Patients receiving antibiotics had a lower risk of treatment incompletion than those in the placebo group (RR 0.64, 95% CI 0.52 to 0.78; 13 trials, 5573 participants; moderate certainty) and were 27% less likely to have persistent clinical infection (RR 0.73, 95% CI 0.65 to 0.81; 19 trials, 5280 participants; moderate certainty). There was no evidence of serious systemic side effects reported in either the antibiotic or placebo group (very low certainty). When compared with placebo, FQs (RR 0.70, 95% CI 0.54 to 0.90) but not non-FQs (RR 4.05, 95% CI 1.36 to 12.00) may result in fewer participants with ocular side effects. However, the estimated effects were of very low certainty. AUTHORS' CONCLUSIONS: The findings of this update suggest that the use of topical antibiotics is associated with a modestly improved chance of resolution in comparison to the use of placebo. Since no evidence of serious side effects was reported, use of antibiotics may therefore be considered to achieve better clinical and microbiologic efficacy than placebo. Increasing the proportion of participants with clinical cure or increasing the speed of recovery or both are important for individual return to work or school, allowing people to regain quality of life. Future studies may examine antiseptic treatments with topical antibiotics for reasons of cost and growing antibiotic resistance.

Association between teeth loss and nasogastric tube feeding dependency in older adults from Taiwan: a retrospective cohort study.

BACKGROUND: To examine the association between teeth loss and nasogastric tube feeding dependency in older people. METHODS: The National Health Interview Survey (NHIS) 2005, 2009, and 2013 in Taiwan. Participants were selected by a multistage stratified sampling method and baseline characteristics, including socioeconomic status and health habits, were obtained by well-trained interviewers. The NHIS was linked with the National Health Insurance research database 2000-2016 and the National Deaths Dataset, which contains all the medical information of ambulatory and inpatient care. Cox regression was used to examine the association between the number of teeth lost and nasogastric tube feeding dependency. RESULTS: There were 6165 adults older than 65 years old enrolled in the analysis, with 2959 male (48%) and the mean (SD) age was 73.95(6.46) years old. The mean follow-up duration was 6.5(3.3) years. Regarding the teeth loss categories, 1660 (26.93%), 2123 (34.44%), and 2382 (38.64%) of participants were categorized as having no teeth loss, loss of 1-9 teeth, and loss of 10-28 teeth, respectively. During 39,962 person-years of follow-up, new-onset nasogastric feeding dependency was recognized in 220(13.25%), 256(12.06%), and 461(19.35%) participants who were categorized as having no teeth loss, loss of 1-9 teeth, and loss of 10-28 teeth, respectively. Kaplan-Meier curves demonstrated significant findings (Log-rank P < 0.01). After potential confounders were adjusted, compared with those without teeth loss, older adults who had lost 10-28 teeth had significantly increased risks of occurrence nasogastric feeding dependency (AHR, 1.31; 95% CI, 1.05-1.62; p-value = 0.02). Furthermore, a significant dose-response relation between the number of teeth lost and increased risk of nasogastric feeding was found (p for trend< 0.01). CONCLUSIONS: Older adults who had lost 10-28 teeth had a significantly increased risk of nasogastric tube feeding dependency. Early identification of the oral disease is crucial for the prevention of the occurrence of teeth loss and the following nutrition problems, which would reduce risk of nasogastric tube feeding dependency.

The association of dry eye syndrome and psychiatric disorders: a nationwide population-based cohort study.

BACKGROUND: Several previous studies reported a greater prevalence of dry eye syndrome (DES) among patients with psychiatric diseases. The aim of this study is to investigate the prevalence and risk factors of DES in patients with psychiatric disorders (PD) using nationwide population-based data in Taiwan. METHODS: This population-based cohort study retrospectively identified patients with PD from 1997 to 2011. Patients with both PD and DES served as the DES cohort, and PD patients without DES comprised the non-DES cohort. PD was defined as a diagnosis of PD (ICD-9-CM 290-319) made by psychiatrists only, with at least three consecutive outpatient visits or at least one inpatient visit. DES was defined as a diagnosis of DES (ICD-9-CM 375.15) and a prescription for an eye lubricant (anatomical therapeutic chemical code, ATC code: S01XA). The main outcome measures were the prevalence of DES in these patients and associated risk factors. RESULTS: A total of 75,650 patients with PD (3665 in the DES cohort and 71,985 in the non-DES cohort) were included in the final analysis. The majority of patients in the DES group were women (72.6%), compared the non-DES group (57.8%). The mean age of patients in the DES cohort was 62.2 ± 14.9, which was significantly older than those in the non-DES group (50.9 ± 17.5). The patients with DES had a significantly greater likelihood of having dementia, bipolar disorder, depression, and neurotic disorders. Conditional regression analyses revealed that patients with dry eye disease were more likely to have schizophrenia (OR = 1.34), bipolar disorder (OR = 1.9), depression (OR = 1.54), and neurotic disorders (OR = 1.62). In addition, patients with DES were more likely to use 1st generation anti-psychotics (OR = 1.28) and had a lower risk of using 2nd generation anti-psychotics (OR = 0.64). CONCLUSION: The study demonstrated that among PD patients, DES is highly prevalence in certain subtypes of PD, such as depression, bipolar disorder, and neurotic disorders, after adjusting for the comorbidities.

Repeated intravitreal injections of antivascular endothelial growth factor in patients with neovascular age-related macular degeneration may increase the risk of ischemic optic neuropathy.

BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.

Porphyromonas gingivalis Gingipains Display Transpeptidation Activity.

Porphyromonas gingivalis is a keystone periodontal pathogen that has been associated with autoimmune disorders. The cell surface proteases Lys-gingipain (Kgp) and Arg-gingipains (RgpA and RgpB) are major virulence factors, and their proteolytic activity is enhanced by small peptides such as glycylglycine (GlyGly). The reaction kinetics suggested that GlyGly may function as an acceptor molecule for gingipain-catalyzed transpeptidation. Purified gingipains and P. gingivalis whole cells were used to digest selected substrates including human hemoglobin in the presence or absence of peptide acceptors. Mass spectrometric analysis of the substrates digested with gingipains in the presence of GlyGly showed that transpeptidation outcompeted hydrolysis, whereas the trypsin-digested controls exhibited predominantly hydrolysis activity. The transpeptidation levels increased with increasing concentration of GlyGly. Purified gingipains and whole cells exhibited extensive transpeptidation activities on human hemoglobin. All hemoglobin cleavage sites were found to be suitable for GlyGly transpeptidation, and this transpeptidation enhanced hemoglobin digestion. The transpeptidation products were often more abundant than the corresponding hydrolysis products. In the absence of GlyGly, hemoglobin peptides produced during digestion were utilized as acceptors leading to the detection of up to 116 different transpeptidation products in a single reaction. P. gingivalis cells were able to digest hemoglobin faster when acceptor peptides derived from human serum albumin were included in the reaction, suggesting that gingipain-catalyzed transpeptidation may be relevant for substrates encountered in vivo. The transpeptidation of host proteins in vivo may potentially lead to the breakdown of immunological tolerance, culminating in autoimmune reactions.

Incidence of cardiovascular diseases in a nationwide HIV/AIDS patient cohort in Taiwan from 2000 to 2014.

The purpose of the study was to determine the incidence of cardiovascular disease (CVD) among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (PLWHA) in Taiwan. PLWHA were identified from the Taiwan Centers for Disease Control HIV Surveillance System between 2000 and 2014. To examine the effect of active antiretroviral therapy (HAART) on CVD incidence, incidence densities and standardised incidence rates (SIRs) of CVD were calculated after stratifying PLWHA by HAART. Of 26 272 PLWHA (mean age, 32.3 years) identified, 73.4% received HAART. Compared with general population, SIRs (95% confidence interval) were higher for incident coronary artery disease (1.11 (1.04-1.19)), percutaneous coronary intervention (1.32 (1.18-1.47)), coronary artery bypass surgery (1.47 (1.29-1.66)), sudden cardiac death (3.01 (2.39-3.73)), heart failure (1.50 (1.31-1.70)) and chronic kidney disease (1.95 (1.81-2.10)), but was lower for incident atrial fibrillation (0.53 (0.37-0.73)). Considering the effect of HAART on incident CVD, the SIRs for all-cause, ischaemic and haemorrhagic stroke were higher in PLWHA who did not receive HAART, but were lower in PLWHA who received HAART. PLWHA had higher risks of incident coronary artery disease, percutaneous coronary intervention, coronary artery bypass surgery, sudden cardiac death, heart failure and chronic kidney disease. HAART reduces risks of incident CVD in PLWHA.

The association between glaucoma and risk of depression: a nationwide population-based cohort study.

BACKGROUND: Previous cross-sectional studies revealed a higher prevalence of depression among glaucoma patients. However, cohort studies were in lack to build the risk of incident depression after the diagnosis of glaucoma. The aim of our study was to investigate the association between glaucoma and the subsequent risk of developing depression and to assess risk factors associated with depression in glaucoma patients. METHODS: A population-based retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from January 1, 2001 through December 31, 2011. Glaucoma patients (n = 8777) and age- and gender-matched control subjects without glaucoma (n = 35,108) were enrolled in the study. Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent depression between the glaucoma and control groups. A Cox regression analysis estimated the crude and adjusted hazard ratios (HRs) for depression. Risk factors leading to depression were investigated among the glaucoma patients. RESULTS: Glaucoma patients had a significantly higher cumulative hazard of depression compared to the control group (p-value < 0.0001). The Cox regression model indicated that the glaucoma group had a significantly higher risk of depression (adjusted HR = 1.71). Within the glaucoma group, significant risk factors for depression included age, female, low income, substance abuse, and living alone. However, the use of ß-blocker eye drops and the number of glaucoma medications were not significant risk factors for depression. CONCLUSION: Patients with glaucoma are at significantly greater risk of developing depression. Among glaucoma patients, age, female, low income, substance abuse, and living alone were significant risk factors for depression.

Porphyromonas gingivalis Type IX Secretion Substrates Are Cleaved and Modified by a Sortase-Like Mechanism.

The type IX secretion system (T9SS) of Porphyromonas gingivalis secretes proteins possessing a conserved C-terminal domain (CTD) to the cell surface. The C-terminal signal is essential for these proteins to translocate across the outer membrane via the T9SS. On the surface the CTD of these proteins is cleaved prior to extensive glycosylation. It is believed that the modification on these CTD proteins is anionic lipopolysaccharide (A-LPS), which enables the attachment of CTD proteins to the cell surface. However, the exact site of modification and the mechanism of attachment of CTD proteins to the cell surface are unknown. In this study we characterized two wbaP (PG1964) mutants that did not synthesise A-LPS and accumulated CTD proteins in the clarified culture fluid (CCF). The CTDs of the CTD proteins in the CCF were cleaved suggesting normal secretion, however, the CTD proteins were not glycosylated. Mass spectrometric analysis of CTD proteins purified from the CCF of the wbaP mutants revealed the presence of various peptide/amino acid modifications from the growth medium at the C-terminus of the mature CTD proteins. This suggested that modification occurs at the C-terminus of T9SS substrates in the wild type P. gingivalis. This was confirmed by analysis of CTD proteins from wild type, where a 648 Da linker was identified to be attached at the C-terminus of mature CTD proteins. Importantly, treatment with proteinase K released the 648 Da linker from the CTD proteins demonstrating a peptide bond between the C-terminus and the modification. Together, this is suggestive of a mechanism similar to sortase A for the cleavage and modification/attachment of CTD proteins in P. gingivalis. PG0026 has been recognized as the CTD signal peptidase and is now proposed to be the sortase-like protein in P. gingivalis. To our knowledge, this is the first biochemical evidence suggesting a sortase-like mechanism in Gram-negative bacteria.

Tannerella forsythia Outer Membrane Vesicles Are Enriched with Substrates of the Type IX Secretion System and TonB-Dependent Receptors.

Tannerella forsythia, a Gram-negative oral bacterium closely associated with chronic periodontitis, naturally produces outer membrane vesicles (OMVs). In this study, OMVs were purified by gradient centrifugation, and the proteome was investigated together with cellular fractions using LC-MS/MS analyses of SDS-PAGE fractions, resulting in the identification of 872 proteins including 297 OMV proteins. Comparison of the OMV proteome with the subcellular proteomes led to the localization of 173 proteins to the vesicle membrane and 61 proteins to the vesicle lumen, while 27 substrates of the type IX secretion system were assigned to the vesicle surface. These substrates were generally enriched in OMVs; however, the stoichiometry of the S-layer proteins, TfsA and TfsB, was significantly altered, potentially to accommodate the higher curvature required of the S-layer around OMVs. A vast number of TonB-dependent receptors related to SusC, together with their associated SusD-like lipoproteins, were identified, and these were also relatively enriched in OMVs. In contrast, other lipoproteins were significantly depleted from the OMVs. This study identified the highest number of membrane-associated OMV proteins to date in any bacterium and conclusively demonstrates cargo sorting of particular classes of proteins, which may have significant impact on the virulence of OMVs.

Porphyromonas gingivalis outer membrane vesicles exclusively contain outer membrane and periplasmic proteins and carry a cargo enriched with virulence factors.

Porphyromonas gingivalis, a keystone pathogen associated with chronic periodontitis, produces outer membrane vesicles (OMVs) that carry a cargo of virulence factors. In this study, the proteome of OMVs was determined by LC-MS/MS analyses of SDS-PAGE fractions, and a total of 151 OMV proteins were identified, with all but one likely to have originated from either the outer membrane or periplasm. Of these, 30 exhibited a C-terminal secretion signal known as the CTD that localizes them to the cell/vesicle surface, 79 and 27 were localized to the vesicle membrane and lumen respectively while 15 were of uncertain location. All of the CTD proteins along with other virulence factors were found to be considerably enriched in the OMVs, while proteins exhibiting the OmpA peptidoglycan-binding motif and TonB-dependent receptors were preferentially retained on the outer membrane of the cell. Cryo-transmission electron microscopy analysis revealed that an electron dense surface layer known to comprise CTD proteins accounted for a large proportion of the OMVs' volume providing an explanation for the enrichment of CTD proteins. Together the results show that P. gingivalis is able to specifically concentrate and release a large number of its virulence factors into the environment in the form of OMVs.

Antibiotics Versus Placebo for Acute Bacterial Conjunctivitis: Findings From a Cochrane Systematic Review.

PURPOSE: To summarize key findings from a Cochrane review of the benefits and safety of antibiotic therapy compared with placebo (or vehicle) for acute bacterial conjunctivitis. DESIGN: Systematic review and meta-analysis. METHODS: We included placebo-controlled randomized controlled trials (RCTs) that compared topical antibiotics with placebo. We followed Cochrane methods for trial selection, data extraction, risk of bias assessment, and evidence synthesis. RESULTS: Twenty-one RCTs involving 8805 participants with acute bacterial conjunctivitis were included. Fifteen (71%) RCTs examined fluoroquinolone (FQ) drops, 3 tested macrolides, alone or in combination with steroids, and another 3 compared other non-FQ antibiotics. Intention-to-treat estimates suggested that compared with placebo, antibiotics may increase clinical recovery by 26% (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.09-1.46) at the end of therapy (5 RCTs, 1474 participants). Modified intention-to-treat estimates, in which only participants with laboratory-confirmed bacterial conjunctivitis were analyzed, indicated that antibiotics were associated with 53% higher likelihood of microbiological cure as compared with placebo (RR: 1.53; 95% CI: 1.34-1.74; 10 RCTs, 2827 participants). Non-FQs (RR: 4.05; 95% CI: 1.36-12.00), but not FQs (RR: 0.70; 95% CI: 0.54-0.90), were likely to increase treatment-associated ocular complications such as eye pain, discomfort, and allergic reactions; the certainty of level of evidence was very low. CONCLUSIONS: Moderate level certainty of evidence suggested that antibiotics may increase the likelihood of clinical recovery and microbiological clearance compared with placebo. Very low-level certainty of evidence suggested that antibiotics may be associated with potential harm in patients with acute bacterial conjunctivitis, but the potential risk of bias from study design, inconsistency in outcome measurement, and reporting limit the evidence to very low certainty.

PG0026 is the C-terminal signal peptidase of a novel secretion system of Porphyromonas gingivalis.

Protein substrates of a novel secretion system of Porphyromonas gingivalis contain a conserved C-terminal domain (CTD) of ∼70-80 amino acid residues that is essential for their secretion and attachment to the cell surface. The CTD itself has not been detected in mature substrates, suggesting that it may be removed by a novel signal peptidase. More than 10 proteins have been shown to be essential for the proper functioning of the secretion system, and one of these, PG0026, is a predicted cysteine proteinase that also contains a CTD, suggesting that it may be a secreted component of the secretion system and a candidate for being the CTD signal peptidase. A PG0026 deletion mutant was constructed along with a PG0026C690A targeted mutant encoding an altered catalytic Cys residue. Analysis of clarified culture fluid fractions by SDS-PAGE and mass spectrometry revealed that the CTD was released intact into the surrounding medium in the wild type strain, but not in the PG0026 mutant strains. Western blot experiments revealed that the maturation of a model substrate was stalled at the CTD-removal step specifically in the PG0026 mutants, and whole cell ELISA experiments demonstrated partial secretion of substrates to the cell surface. The CTD was also shown to be accessible at the cell surface in the PG0026 mutants, suggesting that the CTD was secreted but could not be cleaved. The data indicate that PG0026 is responsible for the cleavage of the CTD signal after substrates are secreted across the OM.

Electrophoresis of a pH-regulated zwitterionic nanoparticle in a pH-regulated zwitterionic capillary.

We consider the electrophoresis of a rigid sphere along the axis of a narrow cylindrical capillary; both are pH-regulated and zwitterionic. This extends available analyses in the literature to a more general and realistic case. Adopting a titanium oxide (TiO2) particle in a silicon dioxide (SiO2) capillary as an example, we examine the capillary radius, the solution pH, and the electrolyte concentration (or double-layer thickness) for their influences on the electrophoretic behavior of a particle. Because the pH solution is adjusted by HCl and NaOH, the presence of four kinds of ionic species, namely, H(+), OH(-), Na(+), and Cl(-), should be considered if NaCl is the background electrolyte. This also extends conventional electrophoresis analyses to the case of multiple ionic species. The interactions of the electroosmotic flow, the properties of the particle and the solution, and the capillary wall yield complicated electrophoretic behavior that can be regulated by the solution pH and the background electrolyte concentration. The results gathered are necessary for the future design of nanopore-based electrophoresis devices.

Postoperative radiotherapy alone is as effective as postoperative chemoradiotherapy in patients with pT4aN0 gingival cancer with negative surgical margins.

Background and purpose: This study compared the survival outcomes following postoperative chemoradiotherapy (CCRT) and postoperative radiotherapy (RT) alone for patients with gingival cancer with negative surgical margins and only bone invasion. Materials and methods: Of the 2579 gingival cancer cases reviewed from 2002 to 2018, 156 were enrolled in the study (CCRT: 63 patients; RT: 93 patients). The primary endpoints were the impact of adjuvant treatment (RT vs. CCRT) on overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS). Subgroup analyses were conducted based on surgical margins (<5 mm vs. ≥ 5 mm) and different adjuvant treatments (RT vs. CCRT). Results: Median follow-up time, age, and invasion depth were 88.5 months, 57 years, and 14 mm, respectively. More patients undergoing adjuvant CCRT had surgical margins < 5 mm (47.6% vs. 21.5%, p < 0.01) than those undergoing RT. No significant difference was observed in the 5-year OS, LRRFS, and DMFS of patients undergoing adjuvant RT and CCRT. Although adjuvant RT alone and CCRT provided similar local control for patients with surgical margins ≥ 5 mm, worse LRRFS trends were observed in patients with surgical margins < 5 mm (hazards ratio, 6.15, 95% confidence interval 0.92-41.13, p = 0.06). Conclusion: Postoperative RT alone may be effective for patients with gingival cancer with negative surgical margins (≥5 mm) and only bone invasion, while postoperative CCRT may result in better LRRFS than RT alone for patients with surgical margins < 5 mm.

Differential proteomic analysis of a polymicrobial biofilm.

Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia exist in a polymicrobial biofilm associated with chronic periodontitis. The aim of this study was to culture these three species as a polymicrobial biofilm and to determine proteins important for bacterial interactions. In a flow cell all three species attached and grew as a biofilm; however, after 90 h of culture P. gingivalis and T. denticola were closely associated and dominated the polymicrobial biofilm. For comparison, planktonic cultures of P. gingivalis and T. denticola were grown separately in continuous culture. Whole cell lysates were subjected to SDS-PAGE, followed by in-gel proteolytic H2¹6O/H2¹8O labeling. From two replicates, 135 and 174 P. gingivalis proteins and 134 and 194 T. denticola proteins were quantified by LC-MALDI TOF/TOF MS. The results suggest a change of strategy in iron acquisition by P. gingivalis due to large increases in the abundance of HusA and HusB in the polymicrobial biofilm while HmuY and other iron/haem transport systems decreased. Significant changes in the abundance of peptidases and enzymes involved in glutamate and glycine catabolism suggest syntrophy. These data indicate an intimate association between P. gingivalis and T. denticola in a biofilm that may play a role in disease pathogenesis.

The outer membrane protein LptO is essential for the O-deacylation of LPS and the co-ordinated secretion and attachment of A-LPS and CTD proteins in Porphyromonas gingivalis.

Protein substrates of a novel secretion system of Porphyromonas gingivalis contain a conserved C-terminal domain (CTD) essential for secretion and attachment to the cell surface. Inactivation of lptO (PG0027) or porT produced mutants that lacked surface protease activity and an electron-dense surface layer. Both mutants showed co-accumulation of A-LPS and unmodified CTD proteins in the periplasm. Lipid profiling by mass spectrometry showed the presence of both tetra- and penta-acylated forms of mono-phosphorylated lipid A in the wild-type and porT mutant, while only the penta-acylated forms of mono-phosphorylated lipid A were found in the lptO mutant, indicating a specific role of LptO in the O-deacylation of mono-phosphorylated lipid A. Increased levels of non-phosphorylated lipid A and the presence of novel phospholipids in the lptO mutant were also observed that may compensate for the missing mono-phosphorylated tetra-acylated lipid A in the outer membrane (OM). Molecular modelling predicted LptO to adopt a ß-barrel structure characteristic of an OM protein, supported by the enrichment of LptO in OM vesicles. The results suggest that LPS deacylation by LptO is linked to the co-ordinated secretion of A-LPS and CTD proteins by a novel secretion and attachment system to form a structured surface layer.

Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity.

Porphyromonas gingivalis is a bacterial pathogen associated with chronic periodontitis that results in destruction of the tooth's supporting tissues. The major virulence determinants of P. gingivalis are its cell surface Arg- and Lys-specific cysteine proteinases, RgpA/B and Kgp. Lactoferrin (LF), an 80-kDa iron-binding glycoprotein found in saliva and gingival crevicular fluid, is believed to play an important role in innate immunity. In this study, bovine milk LF displayed proteinase inhibitory activity against P. gingivalis whole cells, significantly inhibiting both Arg- and Lys-specific proteolytic activities. LF inhibited the Arg-specific activity of purified RgpB, which lacks adhesin domains, and also inhibited the same activity of the RgpA/Kgp proteinase-adhesin complexes in a time-dependent manner, with a first-order inactivation rate constant (k(inact)) of 0.023 min(-1) and an inhibitor affinity constant (K(I)) of 5.02 µM. LF inhibited P. gingivalis biofilm formation by >80% at concentrations above 0.625 µM. LF was relatively resistant to hydrolysis by P. gingivalis cells but was cleaved into two major polypeptides (53 and 33 kDa) at R(284) to S(285), as determined by in-source decay mass spectrometry; however, these polypeptides remained associated with each other and retained inhibitory activity. The biofilm inhibitory activity of LF against P. gingivalis was not attributed to direct antibacterial activity, as LF displayed little growth inhibitory activity against planktonic cells. As the known RgpA/B and Kgp inhibitor N-α-p-tosyl-l-lysine chloromethylketone also inhibited P. gingivalis biofilm formation, the antibiofilm effect of LF may at least in part be attributable to its antiproteinase activity.

Patients with Retinitis Pigmentosa May Have a Higher Risk of Developing Open-Angle Glaucoma.

Background: Retinitis pigmentosa (RP) is the most common retinal hereditary dystrophy, which can lead to blindness if it progresses. Similarly, open-angle glaucoma (OAG) is a genetic disorder. The similarities in genetic variants and pathophysiology between RP and OAG have been reported. We sought to explore whether patients with RP have a significantly higher risk of OAG development. Methods: We enrolled patients with RP into the RP group through Taiwan's National Health Insurance Research Database from 2001 to 2013; we included a comparison group of 1 : 4 age- and gender-matched individuals without RP. We performed a Cox regression analysis to estimate the crude and adjusted hazard ratios (HRs) for OAG. We adjusted the following confounders in the Cox regression model: age, gender, diabetes mellitus, hypertension, and chronic kidney disease. Results: We enrolled 6,223 subjects with RP and 24,892 subjects for comparison. The mean age of the cohort was 49.0 ± 18.1 years. The RP group had significantly higher percentages of diabetes mellitus, hypertension, and hyperlipidaemia. The cumulative incidence of OAG in patients with RP was 1.57%; this was significantly higher than that in the comparison group (0.58%, p < 0.0001). On univariate Cox regression analysis, the hazard of OAG development was significantly greater in the RP group than in the comparison group with an unadjusted HR of 2.86 (95% confidence interval, 2.21-3.70). The increased risk persisted after adjusting for confounders (adjusted HR = 2.86; 95% CI, 2.21-3.70). Conclusions: This nationwide population-based cohort study showed that people with RP are at a significantly greater risk of developing OAG than individuals without it.

Risk of inflammatory bowel disease in uveitis patients: a population-based cohort study.

OBJECTIVES: To investigate the potential association between uveitis and an increased risk of developing inflammatory bowel disease (IBD). METHODS: We conducted a retrospective cohort study by interrogating data from the Taiwan National Health Insurance Research Database entered between January 1, 2001 and December 31, 2013 to identify uveitis patients and age- and gender-matched controls. The cumulative incidence rates of subsequent IBD in the two groups were compared. The adjusted hazard ratio (HR) of IBD related to uveitis was generated by a multivariate cox regression model after adjustment for hypertension, diabetes, hyperlipidaemia, obesity and smoking. Furthermore, the HRs of the Crohn's disease (CD) and ulcerative colitis (UC) IBD subtypes were calculated separately. RESULTS: A total of 198,923 subjects with uveitis and 397,846 controls were enroled. The mean age of the cohort was 47.7 ± 18.9 years. A significantly higher cumulative incidence of IBD was found in the uveitis group than in controls (4.13% vs. 1.48%, p < 0.0001). Under univariate cox regression analysis, uveitis patients had a significantly higher risk of IBD (HR = 1.47; 95% confidence interval (CI): 1.43-1.52, p < 0.0001). The association remained significant in the multivariate regression model, with an adjusted HR of 1.44 (95% CI: 1.39-1.49, p < 0.0001). Moreover, in subgroup analysis, uveitis was significantly associated with an increased risk of Crohn's disease (adjusted HR = 1.49; 95% CI: 1.44-1.54), but not with ulcerative colitis (adjusted HR = 1.03; 95% CI: 0.92-1.15). CONCLUSIONS: Patients with uveitis are at significantly greater risk of developing IBD than individuals without uveitis.