Increased Risk of Primary Sj?gren's Syndrome in Female Patients with Thyroid Disorders: A Longitudinal Population-Based Study in Taiwan

Background

A number of reports have indicated an association between thyroid diseases and primary Sjögren''s syndrome (pSS). However, fewer studies have investigated whether the presence of thyroid diseases is associated with increased risk of developing pSS. Thus, the aim of our study was to use a nationwide health claims database to explore the prevalence and risk of pSS in female patients with thyroid diseases.

Methods

From the Registry of Catastrophic Illness database in the National Health Insurance Research Database in Taiwan, we identified 389 female patients with a diagnosis of pSS from 2005 to 2010. We also obtained 1945 control subjects frequency-matched on sex, 10-year age interval, and year of index date from the Longitudinal Health Insurance Database (LHID2000). Both groups were retrospectively traced back to a period of eight years to obtain diagnosis of thyroid diseases prior to index date.

Results

A significantly higher risk of pSS was associated with the presence of thyroid diseases (adjusted odds ratio (AOR) = 2.1, 95% confidence interval (CI) = 1.6–2.9). Among the sub-categories of thyroid diseases, patients with thyroiditis (AOR = 3.6, 95% CI = 1.7–7.5), thyrotoxicosis (AOR = 2.5, 95% CI = 1.6–3.8), and unspecified hypothyroidism (AOR = 2.4, 95% CI = 1.2–4.6), and simple and unspecified goiter (AOR = 2.0, 95% CI = 1.3–3.3) were significantly associated with increased risk of pSS. The associations were generally stronger in the mid-forties to mid-sixties age group, except in patients with unspecified hypothyroidism.

Conclusions

The risk of pSS was significantly increased in female patients with thyroid diseases, particularly those in their mid-forties to mid-sixties. An increased awareness of the possibility of pSS in perimenopausal females with thyroid diseases is important to preserve their quality of life and to avoid comorbidity.     

The Post-Resuscitative Urinalysis Associate the Survival of Patients with Non-Traumatic Out-of-Hospital Cardiac Arrest

Objective

To analyze whether urine output and urinalysis results are predictive of survival and neurologic outcomes in patients with non-traumatic out-of-hospital cardiac arrest (OHCA).

Methods

Information was obtained from 1,340 patients with non-traumatic OHCA who had achieved a sustained return of spontaneous circulation (ROSC). Factors that were associated with survival in the post-resuscitative period were evaluated. The association between urine output and fluid challenge in the early resuscitative period was analyzed and compared between the survivors and the non-survivors. The results of the initial urinalysis, including the presence of proteinuria and other findings, were used to evaluate the severity of vascular protein leakage and survival. The association between proteinuria and the neurologic outcomes of the survivors was also analyzed. The clinical features of capillary leakage were examined during the post-resuscitative period.

Results

Of the 1,340 patients, 312 survived. A greater urine output was associated with a higher chance of survival. The initial urine output increased in proportion to the amount of fluid that was administered during early resuscitation in the emergency department for the survivors but not for the non-survivors (p<0.05). In the initial urinalysis, proteinuria was strongly associated with survival, and severe proteinuria indicated significantly poorer neurologic outcomes (p<0.05 for both comparisons). Proteinuria was associated with a risk of developing signs of capillary leakage, including body mass index gain and pitting edema (both p<0.001).

Conclusion

The severity of proteinuria during the early post-resuscitative period was predictive of survival.     

Analysis of Variations in the Glutamate Receptor,N-Methyl D-Aspartate 2A (GRIN2A) Gene Reveals Their Relative Importance as Genetic Susceptibility Factors for Heroin Addiction

The glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene that encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor was recently shown to be involved in the development of opiate addiction. Genetic polymorphisms in GRIN2A have a plausible role in modulating the risk of heroin addiction. An association of GRIN2A single-nucleotide polymorphisms (SNPs) with heroin addiction was found earlier in African Americans. To identify markers that contribute to the genetic susceptibility to heroin addiction, we examined the potential association between heroin addiction and forty polymorphisms of the GRIN2A gene using the MassARRAY system and GeneScan in this study. The frequency of the (GT)26 repeats (rs3219790) in the heroin addiction group was significantly higher than that in the control group (χ² = 5.360, P = 0.021). The allele frequencies of three polymorphisms (rs1102972, rs1650420, and rs3104703 in intron 3) were strongly associated with heroin addiction (P<0.001, 0.0002, and <0.001, after Bonferroni correction). Three additional SNPs from the same intron (rs1071502, rs6497730, and rs1070487) had nominally significant P values for association (P<0.05), but did not pass the threshold value. Haplotype analysis revealed that the G-C-T-C-C-T-A (block 6) and T-T (block 10) haplotypes of the GRIN2A gene displayed a protective effect (P = <0.001 and 0.003). These findings point to a role for GRIN2A polymorphisms in heroin addiction among the Han Chinese from Shaanxi province, and may be informative for future genetic or neurobiological studies on heroin addiction.     

Hemoglobin Levels and Weaning Outcome of Mechanical Ventilation in Difficult-To-Wean Patients: A Retrospective Cohort Study

Introduction

The effect of hemoglobin levels on the weaning outcomes of mechanically ventilated patients remains under debate, particularly for the patients with difficult weaning. This study aims to evaluate the effect of hemoglobin levels on weaning outcomes in difficult-to-wean patients.

Methods

This retrospective cohort study was conducted in a university-affiliated teaching hospital in Taiwan. Patients who fulfilled the criteria of difficult weaning were enrolled. Medical records were reviewed to obtain data on hemograms, biochemistry tests, transfusion records, comorbidities and weaning outcome. The association between hemoglobin levels and 30-day weaning outcomes was evaluated using a logistic regression model.

Results

A total of 751 patients received mechanical ventilation during the study period, 138 of whom fulfilled the criteria of difficult weaning. Compared with the patients whose hemoglobin was <8 g/dL, those with higher hemoglobin levels were more likely to be successfully weaned (odds ratio [OR], 3.69; 95% CI, 1.22–11.15 for hemoglobin 8–10 g/dL and OR, 4.16, 95% CI, 1.30–13.29 for hemoglobin >10 g/dL). Multivariate analysis showed that the odds ratio for weaning success remained significant for hemoglobin levels of 8–10 g/dL (adjusted OR, 3.3; 95% CI, 1.07–10.15) with borderline significance for hemoglobin level > 10 g/dL (adjusted OR, 2.95, 95% CI, 0.88–9.96).

Conclusions

Hemoglobin level is independently associated with weaning outcome in difficult-to-wean patients. Further studies are needed to evaluate whether a restrictive transfusion trigger for acute critical illness is also appropriate for such patients.     

Role of HLA-DP Polymorphisms on Chronicity and Disease Activity of Hepatitis B Infection in Southern Chinese

Background and Aims

The association between HLA-DP single nucleotide polymorphisms (SNPs) and chronic hepatitis B virus (HBV) infection varies between different populations. We aimed to study the association between HLA-DP SNPs and HBV infection and disease activity in the Chinese population of Hong Kong.

Methods

We genotyped SNPs rs3077 (near HLA-DPA1) and rs9277378 and rs3128917 (both near HLA-DPB1) in 500 HBV carriers (hepatitis B surface antigen [HBsAg]-positive), 245 non-HBV infected controls (HBsAg- and antibody to hepatitis B core protein [anti-HBc]-negative), and 259 subjects with natural HBV clearance (HBsAg-negative, anti-HBc-positive). Inactive HBV carriers state was defined by HBV DNA levels <2,000 IU/ml and persistently normal alanine aminotransferase level for least 12 months.

Results

Compared to the non-HBV infected subjects, the HBV carriers had a significantly lower frequency of the rs3077 T allele (p = 0.0040), rs9277378 A allele (p = 0.0068) and a trend for lower frequency of rs3128917 T allele (p = 0.054). These alleles were associated with an increased chance of HBV clearance (rs3077: OR = 1.41, p = 0.0083; rs9277378: OR = 1.61, p = 0.00011; rs3128917: OR = 1.54, p = 0.00017). Significant associations between HLA-DP genotypes and HBV clearance were also found under different genetic models. Haplotype TAT was associated with an increased chance of HBV clearance (OR = 1.64, p = 0.0013). No association was found between these SNPs and HBV disease activity.

Conclusion

HLA-DP SNPs rs3077, rs9277378 and rs3128917 were associated with chronicity of HBV disease in the Chinese. Further studies are required to determine whether these SNPs influence the disease endemicity in different ethnic populations.     

Targeted Delivery of an Antigenic Peptide to the Endoplasmic Reticulum: Application for Development of a Peptide Therapy for Ankylosing Spondylitis

The development of suitable methods to deliver peptides specifically to the endoplasmic reticulum (ER) can provide some potential therapeutic applications of such peptides. Ankylosing spondylitis (AS) is strongly associated with the expression of human leukocytic antigen-B27 (HLA-B27). HLA-B27 heavy chain (HC) has a propensity to fold slowly resulting in the accumulation of misfolded HLA-B27 HC in the ER, triggering the unfolded protein response, and forming a homodimer, (B27-HC)₂. Natural killer cells and T-helper 17 cells are then activated, contributing to the major pathogenic potentials of AS. The HLA-B27 HC is thus an important target, and delivery of an HLA-B27-binding peptide to the ER capable of promoting HLA-B27 HC folding is a potential mechanism for AS therapy. Here, we demonstrate that a His₆-ubiquitin-tagged Tat-derived peptide (THU) can deliver an HLA-B27-binding peptide to the ER promoting HLA-B27 HC folding. The THU-HLA-B27-binding peptide fusion protein crossed the cell membrane to the cytosol through the Tat-derived peptide. The HLA-B27-binding peptide was specifically cleaved from THU by cytosolic ubiquitin C-terminal hydrolases and subsequently transported into the ER by the transporter associated with antigen processing. This approach has potential application in the development of peptide therapy for AS.     

Ocular Injury by Transient Formaldehyde Exposure in a Rabbit Eye Model

Formaldehyde (FA) is frequently used in sterilizing surgical instruments and materials. Exposure to FA is highly concerned for eye tissues. Rabbit corneal epithelial cells were examined for changes after FA exposure. Our results showed that cell survival decreased 7 days after transient 3 min exposure to more than 100 ppm FA by trypan blue staining while MTT assay detected significant decrease at 20 ppm at 24 hours observation. The decrease of cell survival rate was concentration (up to 600 ppm)- and observation time (1–7 day)- dependent. The cell number decreased after 100 ppm FA exposure for more than 10 min at 7-day observation. The FA treated cells showed increased apoptosis/necrosis and cell cycle accumulation at sub G1 phase as well as mitochondria clustering around nucleus. The in vivo rabbit eye exposure for tear production by Schirmer’s test revealed that the FA-induced overproduction of tear also exhibited observation time (1–10 day)- and FA concentration (20–300 ppm for 5 min exposure)-dependent. Activated extracellular signal-regulated kinase (pERK2) in cornea explants by western blotting was reduced and increased c-Jun amino - terminal kinase (JNK) activation (pJNK) in cornea and conjunctiva was evident at 2 month after exposure to 50–200 ppm FA for 5 min. In conclusion, injury to the eye with transient exposure of up to 100 ppm FA for 3 min decreased corneal cell survival while a more sensitive MTT test detected the cell decrease at 20 ppm FA exposure. Morphology changes can be observed even at 5 ppm FA exposure for 3 min at 7 days after. The FA exposure also increased apoptotic/necrotic cells and sub-G1 phase in cell cycle. Long term effect (2 months after exposure) on the eye tissues even after the removal of FA can be observed with persistent JNK activation in cornea and conjunctiva.     

Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1^+/+ and Abca1^−/− mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.