Screening of Fracture Risk and Osteoporosis Among Older Long-term Care Residents: A Prospective Study.

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.

Mucin 5AC is significantly upregulated in exosomes from the nasal lavage fluid and may promote the expression of COX-2, VEGF and MMP-9: an implication in nasal polyp pathogenesis.

BACKGROUND: Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP). METHODS: Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively. RESULTS: Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9. CONCLUSIONS: Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.

Colistin and tylosin enhances disaccharidase activities, and improves morphology and permeability of the intestine of broilers.

1. The present study focused on the potential effects of antibiotics on intestinal digestion and integrity in broilers in terms of disaccharidase activity, electrophysiological properties and morphology. 2. One-day-old Arbour Acres birds were randomly allocated to one of four treatment groups for 42 days; control, colistin (20 mg/kg), tylosin (55 mg/kg) or chlortetracycline (CTC, 55 mg/kg) groups. Colistin and tylosin supplementation, but not CTC supplementation, caused an increase in body weight gain. 3. Colistin and tylosin elevated the activities of maltase and sucrase in the mucosa of the jejunum on d 42. Age caused a gradual decrease in the short-circuit current (Isc) and conductance (Gt) of the ileum, as a measure of permeability. The Isc and Gt of the ileum were higher in the colistin-supplemented broilers than in the control birds on d 42. Tylosin- and CTC-supplemented birds displayed Isc and Gt values similar to those of the control birds. 4. Colistin supplementation increased the villus area in the jejunum and thinned the muscularis mucosae in the ileum compared with the control group. Tylosin supplementation decreased the thickness of the muscularis mucosae and the depth of crypt in the jejunum. CTC thickened the muscularis mucosae in the jejunum and ileum. 5. Colistin and tylosin exhibited a beneficial effect on intestinal digestion and integrity by enhancing disaccharidase activities and improving gut morphology and permeability.

Generic velpatasvir plus sofosbuvir for hepatitis C virus infection in patients with or without human immunodeficiency virus coinfection.

BACKGROUND: Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human immunodeficiency virus (HIV) coinfection. AIM: To evaluate the effectiveness and safety of generic VEL/SOF-based therapy for HCV infection in patients with or without HIV coinfection in Taiwan. METHODS: Sixty-nine HIV/HCV-coinfected and 159 HCV-monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti-viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12 ) were analysed. RESULTS: The SVR12 was achieved in 67 HIV/HCV-coinfected patients (97.1%; 95% CI: 90.0%-99.2%) and in 156 HCV-monoinfected patients (98.1%; 95% CI: 94.6%-99.4%) receiving VEL/SOF-based therapy, respectively. The SVR12 rates were comparable between HIV/HCV-coinfected and HCV-monoinfected patients, regardless of pre-specified baseline characteristics. One hundred twenty-two (53.5%) and seven (3.1%) patients had baseline resistance-associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV-coinfected and HCV-monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV-coinfected patients receiving anti-retroviral therapy containing tenofovir disoproxil fumarate (TDF). CONCLUSIONS: Generic VEL/SOF-based therapy is well-tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.

Spontaneous retropharyngeal emphysema: A case report.

Retropharyngeal emphysema is usually secondary to trauma, iatrogenic injury, and obstructive respiratory diseases. Without prompt and adequate treatment, severe complication such as airway compromise may occur. Spontaneous retropharyngeal emphysema, defined by the presence of free air in the retropharyngeal space without any precipitating cause, is a rare clinical condition in pediatric otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia, and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema.

Prolonged postprocedural outbreak of Mycobacterium massiliense infections associated with ultrasound transmission gel.

Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case-control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case-control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p <0.05) with acquiring the outbreak strain. Isolates from the cases and unopened bottles of ultrasound transmission gel were all of strain ST48 and indistinguishable or closely related by pulsed-field gel electrophoresis. After replacement of contaminated gel, no new cases were detected during 18 months' follow-up. This investigation identified the use of contaminated gel as the common source causing an outbreak on a larger scale than had been recognized. Our findings halted production by the manufacturer and prompted revision of hospital guidelines.

Improvement of glycemic control in streptozotocin-induced diabetic rats by Atlantic salmon skin gelatin hydrolysate as the dipeptidyl-peptidase IV inhibitor.

In our previous study, Atlantic salmon skin gelatin hydrolysed with flavourzyme possessed 42.5% dipeptidyl-peptidase (DPP)-IV inhibitory activity at a concentration of 5 mg mL(-1). The oral administration of the hydrolysate (FSGH) at a single dose of 300 mg per day in streptozotocin (STZ)-induced diabetic rats for 5 weeks was evaluated for its antidiabetic effect. During the 5-week experiment, body weight increased, and the food and water intake was reduced by FSGH in diabetic rats. The daily administration of FSGH for 5 weeks was effective for lowering the blood glucose levels of diabetic rats during an oral glucose tolerance test (OGTT). After the 5-week treatment, plasma DPP-IV activity was inhibited; the plasma activity of glucagon-like peptide-1 (GLP-1), insulin, and the insulin-to-glucagon ratio were increased by FSGH in diabetic rats. The results indicate that FSGH has the function of inhibiting GLP-1 degradation by DPP-IV, resulting in the enhancement of insulin secretion and improvement of glycemic control in STZ-induced diabetic rats.

Unexpectedly high prevalence of Treponema pallidum infection in the oral cavity of human immunodeficiency virus-infected patients with early syphilis who had engaged in unprotected sex practices.

Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, from the oral cavities of 240 patients with 267 episodes of syphilis who reported engaging in unprotected sex practices. The detected treponemal DNA was subjected to genotyping. All of the syphilis cases occurred in men who have sex with men (MSM), and 242 (90.6%) occurred in human immunodeficiency virus-infected patients. The stages of syphilis included 38 cases (14.2%) of primary syphilis of the genital region, 76 (28.5%) of secondary syphilis, 21 (7.9%) of primary and secondary syphilis, 125 (46.8%) of early latent syphilis, and seven (2.6%) others. Concurrent oral ulcers were identified in 22 cases (8.2%). Treponemal DNA was identified from the swabs of 113 patients (42.2%), including 15 (68.2%) with oral ulcers. The most common genotype of T. pallidum was 14f/f. The presence of oral ulcers was associated with identification of T. pallidum in the swab specimens (15/22 (68.2%) vs. 98/245 (40.0%)) (p = 0.01). In multivariate analysis, secondary syphilis (adjusted OR 6.79; 95% CI 1.97-23.28) and rapid plasma reagin (RPR) titres of ≥1: 32 (adjusted OR 2.23; 95% CI 1.02-4.89) were independently associated with the presence of treponemal DNA in patients without oral ulcers. We conclude that detection of treponemal DNA in the oral cavity with PCR assays is not uncommon in MSM, most of whom reported having unprotected oral sex. Although the presence of oral ulcers is significantly associated with detection of treponemal DNA, treponemal DNA is more likely to be identified in patients without oral ulcers who present with secondary syphilis and RPR titres of ≥1: 32.

Scoring systems for 6-month mortality in critically ill cirrhotic patients: a prospective analysis of chronic liver failure - sequential organ failure assessment score (CLIF-SOFA).

BACKGROUND: Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. The Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) score, a modified Sequential Organ Failure Assessment (SOFA) score, is a newly developed scoring system exclusively for patients with end-stage liver disease. AIM: To externally validate the efficacy of the CLIF-SOFA score and evaluate other scoring systems for 6-month mortality in critically ill cirrhotic patients. METHODS: This study prospectively recorded and analysed the data for 30 demographical parameters and some clinical characteristic variables on day 1 of 250 cirrhotic patients admitted to a 10-bed specialised hepatogastroenterology ICU in a 2000-bed tertiary care referral hospital during the period from September 2010 to August 2013. RESULTS: The overall in-hospital and 6-month mortality rate were 58.8% (147/250) and 78.0% (195/250), respectively. Liver diseases were mostly attributed to hepatitis B virus infection (32%). Multiple Cox logistic regression hazard analysis revealed that Glasgow coma scale, both the CLIF-SOFA and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of ICU admission were independent predictors of 6-month mortality. Analysis of the area under the receiver operating characteristic curve revealed that the CLIF-SOFA score had the best discriminatory power (0.900 ± 0.020). Moreover, the cumulative 6-month survival rates differed significantly for patients with a CLIF-SOFA score ≤11 and those with a CLIF-SOFA score >11 on the ICU admission day. CONCLUSION: Both CLIF-SOFA and APACHE III scores are excellent prognosis evaluation tools for critically ill cirrhotic patients.

Conduction control at ferroic domain walls via external stimuli.

Intriguing functionalities at nano-sized domain walls have recently spawned a new paradigm for developing novel nanoelectronics due to versatile characteristics. In this study, we explore a new scenario to modulate the local conduction of ferroic domain walls. Three controlling parameters, i.e., external electrical field, magnetic field and light, are introduced to the 90° domain walls (90° DWs) of BiFeO3. Electrical modulation is realized by electrical transport, where the mobility of 90° DWs can be altered by gating voltage. We further use the ferromagnetic/antiferromagnetic coupling to reveal the inherent magnetism at the DWs. With an established magnetic nature, magnetotransport has been conducted to introduce magnetic controlling parameter, where a giant positive magnetoresistance change can be observed up to 200%. In addition, light modulated conduction, a core factor for multifunctional applications, is successfully demonstrated (current enhancement by a factor of 2 with 11 W white lamp). These results offer new insights to discover the tunability of domain wall nanoelectronics.

Multicentre surveillance of prevalence of the 23S rRNA A2058G and A2059G point mutations and molecular subtypes of Treponema pallidum in Taiwan, 2009-2013.

Resistance mutations A2058G and A2059G, within the 23S rRNA gene of Treponema pallidum, have been reported to cause treatment failures in patients receiving azithromycin for syphilis. Genotyping of T. pallidum strains sequentially isolated from patients with recurrent syphilis is rarely performed. From September 2009 to August 2013, we collected 658 clinical specimens from 375 patients who presented with syphilis for genotyping to examine the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and tp0548 gene, and to detect A2058G and A2059G point mutations by restriction fragment length polymorphism. Treponemal DNA was identified in 45.2% (n = 298) of the specimens that were collected from 216 (57.6%) patients; 268 (40.7%) specimens tested positive for the 23S rRNA gene, and were examined for macrolide resistance. Two isolates (0.7%) harboured the A2058G mutation, and no A2059G mutation was identified. A total of 14 strains of T. pallidum were identified, with 14f/f (57.5%) and 14b/c (10.0%) being the two predominant strains. Forty patients who presented with recurrent episodes of syphilis had T. pallidum DNA identified from the initial and subsequent episodes, with five cases showing strain discrepancies. One patient had two strains identified from different clinical specimens collected in the same episode. Our findings show that 14f/f is the most common T. pallidum strain in Taiwan, where the prevalence of T. pallidum strains that show A2058G or A2059G mutation remains low. Different genotypes of T. pallidum can be identified in patients with recurrent episodes of syphilis.

Spirochetemia due to Treponema pallidum using polymerase-chain-reaction assays in patients with early syphilis: prevalence, associated factors and treatment response.

Between 2009 and 2013, polymerase-chain-reaction assay was used to detect Treponema pallidum in the blood samples collected from 296 patients with early syphilis (241 being HIV infected) and 102 patients (34.5%) had spirochetemia. The presence of spirochetemia was associated with lower CD4 counts (per 10-cell/mm(3) decrease, adjusted odds ratio (AOR), 1.020; 95% CI, 1.006-1.036) and secondary syphilis (AOR, 4.967; 95% CI, 2.016-12.238). Patients with early latent syphilis were less likely to achieve serological response compared with those with primary or secondary syphilis (AOR, 0.317; 95% CI, 0.142-0.708). However, serological response was not affected by presence of spirochetemia or antibiotic regimens.

Mycobacterial bone marrow infections at a medical centre in Taiwan, 2001-2009.

Mycobacterial bone marrow (BM) infection is the most common diagnosis established by BM examinations for fever of unknown origin. In this study, clinical features and outcomes of patients who fulfilled the criteria for BM infection due to Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) at a medical centre in Taiwan from 2001 to 2009 were investigated. The BM histopathological findings were also analysed. A total of 24 patients (16 men, eight women) with mycobacterial BM infections were found. Of these, nine (38%) were positive for human immunodeficiency virus (HIV) and six (25%) had no pre-existing immunocompromised conditions. MTB isolates were obtained from 11 (46%) patients and NTM species were isolated from 10 (42%) patients, including M. avium complex (MAC, n = 7) and M. kansasii (n = 3). Patients with MTB infections were significantly older than those with NTM infections (60·5 vs. 47·7 years, P = 0·043) and were less likely to have a positive BM culture (45% vs. 100%, P = 0·012). The 90-day survival rates for MTB and NTM BM infections were 68% and 60%, respectively (P = 0·61). In addition, the presence of BM granulomas was significantly more common in patients with MTB BM infections than in those with NTM infections (82% vs. 30%, P = 0·030). In Taiwan, the importance of NTM was not inferior to MTB and besides MAC, M. kansasii might be an important pathogen in non-HIV-infected patients. The presence of BM granulomas and caseation provides valuable information regarding early treatment pending culture results.

Extrapulmonary infections caused by a dominant strain of Mycobacterium massiliense (Mycobacterium abscessus subspecies bolletii).

A single strain of Mycobacterium massiliense (BRA 100), a subspecies of the Mycobacterium abscessus complex, has been responsible for an epidemic of post-surgical infections in Brazil. Outside Brazil, this is the first report to describe a single emerging strain of M. massiliense (TPE 101) associated with extrapulmonary infections. This phenomenon may be underestimated because sophisticated molecular typing of M. abscessus is not routinely performed. Our molecular epidemiology study was triggered by an outbreak investigation. Nine case isolates were grown from the surgical sites of nine mostly paediatric patients receiving operations from 2010 to 2011. All available non-duplicated isolates of M. abscessus during this period were obtained for comparison. Mycobacteria were characterized by multilocus sequence analysis (MLSA), repetitive sequence PCR (rep-PCR) and pulsed-field gel electrophoresis (PFGE). Of 58 isolates of M. abscessus overall, 56 were clinical isolates. MLSA identified 36 of the isolates as M. massiliense. All case isolates were indistinguishable by PFGE and named the TPE 101 pulsotype. Of the stored strains of M. abscessus, TPE 101 strains were over-represented among the control surgical wound (7/7, 100%) and subcutaneous tissue isolates (4/5, 80%) but rare among the respiratory isolates (1/16, 6%) and absent from external skin, ocular and environmental samples. In conclusion, a unique strain of M. massiliense has emerged as a distinctive pathogen causing soft tissue infections in Taiwan. Further study to identify whether this is due to an occult common source or to specific virulence factors dictating tissue tropism is warranted.

Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).

Cyclophilin A and nuclear factor of activated T cells are essential in cyclosporine-mediated suppression of polyomavirus BK replication.

Immunosuppressants have impacts on the development of polyomavirus-associated nephropathy. We previously demonstrated that cyclosporin A (CsA) suppressed polyomavirus BK (BKV) replication. The role of cyclophilin A (CypA) and nuclear factor of activated T cells (NFAT) in CsA-imposed suppression of BKV replication was determined in this study. Results demonstrated that knockdown of CypA but not CypB significantly reduced BKV large T antigen (TAg) expression and BKV titer. Overexpression of CypA reversed CypA siRNA-induced inhibition in BKV TAg expression. In addition, CypA overexpression attenuated the suppressive effect of CsA on TAg expression, suggesting CypA implicated in CsA-mediated anti-BKV effect. Knockdown of NFATc3 abrogated TAg expression, while overexpression of NFATc3 promoted TAg expression and augmented BKV promoter activity. NFATc3 binding to the BKV promoter was verified by chromatin immunoprecipitation assay and electrophoretic mobility shift assay. Renal histology also displayed an increase in NFATc3 expression in tubulointerstitium of BKV-associated nephropathy. Furthermore, overexpression of NFATc3 rescued CsA-mediated inhibition of BKV load and TAg expression. A CsA analog, NIM811, which cannot block NFAT functionality, failed to suppress TAg expression. In conclusion, CypA and NFAT are indispensable in BKV replication. CsA inhibits BKV replication through CypA and NFAT, which may be potential targets of anti-BKV treatment.

The immune reconstitution inflammatory syndrome related to HIV co-infections: a review.

The immune reconstitution inflammatory syndrome (IRIS) is a consequence of an excessive pathogen-specific immune recovery reaction and occurs in a subset of patients on antiretroviral therapy (ART). Infective forms of IRIS may present either as an 'unmasking' of a previously subclinical infection or the paradoxical clinical deterioration of an infection for which the patient received appropriate antimicrobial therapy. The most important risk factors for IRIS are a low CD4+ T-cell count and a short time between treatment of the infection and the commencement of ART. The general approach to the treatment of IRIS is to continue ART and provide antimicrobial therapy for the provoking infection. The majority of cases are self-limiting; however, mortality and hospitalisation rates are particularly high when tuberculosis- or cryptococcal-IRIS affects the central nervous system (CNS). Corticosteroid therapy should be considered in certain forms of IRIS after the exclusion of other conditions that could explain the inflammatory manifestations in the patients. Given that a low CD4+ T-cell count is a major risk factor for the development of IRIS, commencing ART at a CD4+ T-cell count of >350/µL will prevent most cases.

A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity.

The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, P<0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.

Emerging HIV-1 resistance to tipranavir and darunavir in patients with virological failure to first-generation protease inhibitors in Taiwan.

Ritonavir-boosted tipranavir (TPV/r) and darunavir (DRV/r) have been approved in patients with virological resistance to multiple protease inhibitors (PIs). Whether the HIV-1 from these patients with virological failure to first-generation PIs remains susceptible to TPV/r or DRV/r is questionable. The susceptibilities of HIV-1 isolates to second-generation PIs in patients who experienced virological failure in three time periods were analysed: 9-2006 to 4-2007 (period 1), 5-2007 to 12-2007 (period 2) and 1-2008 to 8-2008 (period 3). A total of 53 subjects were enrolled, and 51 subject isolates (96.2%) were resistant to ≥1 PIs. The mutation scores for TPV and DRV, and the percentage of isolates with resistance to TPV or DRV, increased significantly from period 1 to period 3. Our data revealed a significant increase in the levels of genotypic resistance to TPV and DRV over the past two years in patients with virological failure to first-generation PIs.