Association of arytenoid chondritis with equine lymphocyte antigens but no association with laryngeal hemiplegia, umbilical hernias and cryptorchidism

Associations were sought between ELA A1-A10 and W11 antigens and the presence of laryngeal hemiplegia, arytenoid chondritis, umbilical hernias and cryptorchidism in Thoroughbreds and/or Quarter Horses. No significant associations were detected between laryngeal hemiplegia and any ELA antigen in Thoroughbreds. The association between arytenoid chondritis and A9 was significant with a relative risk (RR) of 15.6 and aetiologic fraction (EF) of 0.80 in Thoroughbreds. There were apparent associations based on RR between A4 and A5 in Quarter Horses with umbilical hernias (RR = 7.5 and 6.1 respectively); however, these were not statistically significant. No significant associations were detected with cryptorchidism in Quarter Horses when the control population included both sexes. When only unaffected males were used as the control group, there was an apparent increase in relative risk with A6 (from RR = 1.7 to 4.3); however this was not statistically significant. Cryptorchidism in Thoroughbreds showed an increased relative risk with A5 regardless of whether the control population included males and females (RR = 4.1) or only males (RR = 4.7) but the increases were not statistically significant.     

Effect of breed of horse on muscle carnosine concentration

1. Muscle samples from the M. gluteus medius were obtained from six Quarter Horses (QH), six Thoroughbreds (TB), and five Standardbreds (SB) to determine carnosine values and fiber type percentages. 2. Muscle biopsies were for fiber type percentages and carnosine concentration. 3. QH had a lower percentage of slow twitch oxidative fibers and a higher percentage of past twitch glycolytic fibers than SB or TB. 4. Fast twitch oxidative-glycolytic fibers were lowest in the QH. 5. The QH had mean carnosine values significantly greater (P less than 0.01) than the mean values for SB and TB. 6. Across breeds muscle carnosine concentration was positively correlated (P less than 0.05; r = 0.53) with fast twitch glycolytic fiber percentage and negatively correlated (P less than 0.05, r = -0.51) with fast twitch oxidative fiber percentage. 7. Free intramuscular carnosine is believed to function as an intracellular buffer. Since carnosine was highest in the muscle of horses with the greatest percentage of fast twitch glycolytic fibers, these data are consistent with the proposed function of this dipeptide.     

Assessment of the FAM174A 11G allele as a risk allele for equine metabolic syndrome

An 11G nucleotide repeat in the 3′ UTR of FAM174A was recently postulated as a risk allele with a dominant mode of inheritance for equine metabolic syndrome (EMS) and laminitis status in Arabian horses. The objective of this project was to evaluate this hypothesis in a large and diverse across-breed population. A total of 301 ponies, 292 Morgans, 64 Arabians, 49 Tennessee Walking Horses and 59 Quarter Horses were genotyped for six observed G repeat alleles in the FAM174A 3′ UTR. Phenotype data included laminitis status, baseline insulin, glucose, non-esterified fatty acids, triglycerides, adiponectin, leptin, ACTH, insulin and glucose post oral sugar test, and two proxies for insulin resistance. The 11G allele frequencies were 18.8, 6.9, 1.8, 0.2 and 0.0% in the Arabians, Tennessee Walkers, ponies, Morgans and Quarter Horses respectively. Association analyses between FAM174A genotype and EMS phenotypes, and between allele count and EMS phenotypes, identified no statistically significant associations. When a dominant effect for the 11G allele was evaluated, a statistically significant association with adiponectin levels was identified in the ponies, and pairwise comparisons revealed that the estimated marginal means were higher in ponies with the 11G allele vs. alternative alleles (i.e. the allele had a protective effect). In conclusion, our data do not support the FAM174A 11G allele as a risk allele for EMS in our studied breeds.     

Breed differences in circulating equine relaxin.

Equine relaxin has been previously determined in a small number of pregnant Thoroughbred mares. To better define the normal pregnancy pattern of relaxin, the current study reports on a much larger number of mares. It also was designed to determine if all equids have the same gestational pattern of relaxin secretion. Plasma samples were collected weekly in 24 Standardbred mares, every 7-10 days in 10 pony mares, and daily in late pregnancy from 16 burros. Standardbreds had higher concentrations of relaxin than that reported for Thoroughbreds during most of gestation and did not exhibit the midpregnancy nadir in relaxin concentrations observed in Thoroughbreds. Relaxin concentrations in Standardbreds showed a small but steady decline from Day 150 until delivery. Pony mares had lower relaxin concentrations throughout pregnancy than other mares and had continuously increasing concentrations during gestation. Burros had relaxin concentrations intermediate to ponies and other mares in late gestation. Burros induced to foal with oxytocin showed a sharp increase in relaxin concentrations. No effect of the sex of the offspring was observed in relaxin profiles in Standardbred mares. Each of three Standardbreds with abnormal termination of pregnancy exhibited abnormally low relaxin concentrations at some point in the gestation prior to termination of the pregnancy. Thus, relaxin may be an indicator of placental functioning and used to assess at-risk pregnancies in mares.     

The role of smoking status and collagen IX polymorphisms in the susceptibility to cervical spondylotic myelopathy

We investigated a possible association of collagen IX tryptophan (Trp) alleles (Trp2 and Trp3) and smoking with cervical spondylotic myelopathy (CSM) in 172 Chinese patients and 176 age- and gender-matched controls. The smoking status was evaluated by smoking index (SI). The CSM cases had a significantly higher prevalence of Trp2 alleles (Trp2+) than controls (19.8 vs 6.2%, P = 0.002), but the prevalence of Trp3 alleles (Trp3+) was similar between the two groups (23.3 vs 21.6%, P = 0.713). Logistic regression analyses showed that the subjects with Trp2+ had a higher risk for CSM. We thus analyzed whether smoking status influenced the association between Trp2 alleles and CSM risk. Among Trp2+ subjects with an SI less than 100, the smoking status did not influence the effect of risk for SCM [odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 0.85-2.18, P > 0.05]. When SI increased from 101 to 300, the OR for CSM reached 3.34 (95%CI = 2.11-5.67, P = 0.011); when SI was more than 300, the OR for CSM reached 5.56 (95%CI = 3.62-7.36, P < 0.001). Among Trp2- subjects with SI more than 300, the OR for CSM increased 2.14 (95%CI = 1.15-4.07, P = 0.024). We found a significant association between the Trp2 alleles and CSM risk and smoking amplifies this risk, suggesting that smoking abstinence is important for reducing CSM occurrence in subjects with high genetic risk.     

Twinning in mares: A survey of veterinarians and analyses of theriogenology records

Responses of 22 veterinarians to a questionnaire and the records of three brood-mare farms were examined to obtain information on twinning. The incidence rates of multiple ovulations on the three farms were 9%, 11%, and 22%. The multiple ovulation rate was reduced 42-67% in foaling mares compared to barren and maiden mares. Multiple ovulations were significantly more frequent in Thoroughbreds (19%) than in Quarter Horses (9%) and Appaloosas (8%). Both the questionnaire and the farm records indicated a high degree of repeatability of multiple ovulations and twin pregnancies within mares and within certain family lines. The likelihood of multiple ovulations was approximately doubled when the preceding cycle also had multiple ovulations. On two of the farms, breeding was withheld or postponed until after the first ovulation when multiple follicles were present. There were no significant differences in overall reproductive efficiency (pregnancy and foaling rates) among the three farms and the incidence of observed twin abortions or births was low on all three farms (0.4, 0.2, and 0%, respectively).     

Suicide attempts in the Epidemiologic Catchment Area Study

This study examines risk factors for attempted suicide in the general community. Data from the five-site NIMH Epidemiologic Catchment Area (ECA) Study were used to estimate lifetime prevalence and identify risk factors for suicide attempts. Occurrence of suicide attempts and lifetime diagnosis of psychiatric disorder were ascertained, using the NIMH Diagnostic Interview Schedule (DIS). Of 18,571 adult respondents aged 18 and over, 2.9 percent reported that they had attempted suicide at some time in their lives. A weighted logistic regression model was constructed to ascertain significant (p less than .0028 with Bonferroni correction) risk factors for attempted suicide. Persons who had a lifetime diagnosis of a psychiatric disorder had the highest risk of attempted suicide (odds ratio [OR] = 8.4). Females (OR = 3.3), separated or divorced persons (OR = 2.5), Whites (OR = 1.7), persons in the two lowest socioeconomic quartiles (ORs = 2.2, 2.3), and respondents from the Los Angeles ECA (OR = 1.8) were also more likely to have attempted suicide. These findings contribute to an understanding of suicide and suicidal behavior in general populations, outside the clinical setting.     

Increased Risk of Herpes Zoster in Diabetic Patients Comorbid with Coronary Artery Disease and Microvascular Disorders: A Population-Based Study in Taiwan

We investigated the association between the risk of herpes zoster (HZ) and diabetes-related macrovascular comorbidities and microvascular disorders in diabetic patients. This retrospective study included 25,345 patients with newly identified HZ and age- and gender-matched controls retrieved from the National Health Insurance Research Database in Taiwan during the period of 2005 to 2011. Multivariate logistic regression analyses were used to calculate the odds ratios (OR) and to assess the risk factors for HZ in diabetic patients with associated macrovascular or microvascular disorders. Risk factors for HZ were significantly increased in cases of diabetes mellitus (DM) compared with those in cases of non-DM controls (20.2% vs. 17.0%, OR = 1.24, p<0.001). Results of age- and gender-adjusted analyses demonstrated a significantly higher risk of HZ in DM patients with accompanying coronary artery disease (CAD) (adjusted OR = 1.21, p<0.001) and microvascular disorders (aOR = 1.32, p<0.001) than in DM patients with other comorbidities but no microvascular disorders. Patients who took thiazolidinedione, alpha-glucosidase inhibitors and insulin had a higher HZ risk than those taking metformin or sulphonylureas alone (aOR = 1.11, 1.14 and 1.18, p<0.001, respectively). Patients who took insulin alone or in combination with other antidiabetic agents had a significantly higher risk of HZ (aOR = 1.25, p<0.001) than those who received monotherapy. Diabetic patients comorbid with coronary artery disease and associated microvascular disorders had an increased risk of HZ occurrence.     

The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome

The metabolic syndrome is associated with low high-density lipoprotein-cholesterol (HDL-C) and decreased low-density lipoprotein (LDL) particle size. The Taq1B-polymorphism in the cholesteryl ester-transfer protein (CETP)-gene influences HDL-C, CETP concentration, and LDL-size. We investigated the effect of the Taq1B-polymorphism on the risk of the metabolic syndrome in 1,503 participants (973 men, 530 women) of the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk study. CETP concentration was determined in a subgroup (n = 486) by an enzyme-linked immunosorbent assay. Prevalence of the metabolic syndrome was 16.7% (18.5% in men, 13.5% in women). The Taq1B-polymorphism influenced significantly CETP concentrations, HDL-C levels, and LDL-size (P < 0.001 for all). The relative risk of the metabolic syndrome was reduced by 32% (odds ratio (OR) 0.68 (95% CI: 0.51-0.89), P = 0.005) in carriers of the B2 variant. This risk reduction persisted after adjustment for age and sex (OR 0.69 (0.53-0.92), P = 0.01) and after further adjustment for body mass index, waist-to-hip ratio, blood pressure, insulin resistance (IR), HDL-C, and triglycerides (TGs) (OR 0.43 (0.26-0.72), P = 0.001). Furthermore, the risk reduction was more pronounced in men than in women. We conclude that CETP plays an important role in the metabolic syndrome, possibly involving novel functions of CETP.     

Association of increased heat shock protein 70 levels in the lymphocyte with high risk of adverse pregnancy outcomes in early pregnancy: a nested case-control study

Studies suggest that heat shock proteins (Hsps), Hsp70 in particular, may play a role in embryogenesis and reproduction. As the first trimester is the critical period of human fetal development, we tested whether there is an association between Hsp70 expression in lymphocytes and adverse pregnancy outcomes (APOs) during that period. We measured lymphocyte Hsp70 levels by immunoblot in 55 pregnant women with APOs and 110 well-matched controls selected from 778 pregnant women in a nested case-control study. Multivariate logistic regression models were used to investigate the association between lymphocyte Hsp70 levels and risk of developing APOs. Our data showed that Hsp70 levels in women with APOs, especially those younger than 29 years old, were significantly higher than controls (193 vs 135 units, P < 0.001) and that the elevated Hsp70 levels were associated with a significantly increased risk of APOs (adjusted OR = 1.014; 95% CI = 1.008-1.020, P < 0.001). Our results also showed that the sensitivity, specificity, and positive and negative predictive values were 78%, 60%, 50%, and 85%, respectively, among these pregnant women. Adjusted ORs and 95% CI for the association between a Hsp70 value > 153 IOD and APOs were statistically significant (OR = 8.78, 95% CI = 2.79-27.64, P < 0.001). These results suggest that Hsp70 may play a role in the etiology of APOs. However, the underlying mechanisms for the elevation of Hsp70 in women with APOs and whether Hsp70 can be applied as a clinical indicator of APOs warrant further investigations.     

Functional polymorphism in the EpCAM gene is associated with occurrence and advanced disease status of cervical cancer in Chinese population

The epithelial cell adhesion molecule (EpCAM) was originally identified as a tumor associated antigen, attributable to its high expression on rapidly proliferating tumors of epithelial origin. EpCAM plays vital roles in carcinogenesis, tumor progression and metastasis in most tumors. A non-synonymous polymorphism (rs1126497 C/T) was found in exon 3 of EpCAM, which cause a transition from 115 Met to 115 Thr. Another polymorphism (rs1421 A/G) in the 3'UTR causes loss of has-miR-1183 binding. We performed a multiple independent case-control analysis to assess the association between EpCAM genotypes and cervical cancer risk. Genotyping a total of 518 patients with cervical cancer and 723 control subjects in a Chinese population, we observed that the variant EpCAM genotypes (rs1126497 CT, and TT) were associated with substantially increased risk of cervical cancer. Compared with the rs1126497 CC genotype, CT genotype had a significantly increased risk of cervical cancer (Crude OR = 1.70; 95% CI = 1.33-2.20; adjusted OR = 1.72; 95% CI = 1.33-2.22), the TT carriers had a further increased risk of cervical cancer (Crude OR = 1.94; 95% CI = 1.01-3.72; adjusted OR = 1.96; 95%CI = 1.01-3.81), and there was a trend for an allele dose effect on risk of cervical cancer (P < 0.001). Moreover, the allele T increases the risk for invasive disease or metastatic disease, compared with C allele. However, there exists no significant difference in genotype frequencies of rs1421 A/G site between cases and controls (P = 0.798). These findings suggest that rs1126497 C/T polymorphism in EpCAM may be a genetic modifier for developing cervical cancer.     

Equine sarcoid: BCG immunotherapy compared to cryosurgery in a prospective randomised clinical trial

Summary A total of 30 horses with single or multiple sarcoid tumors of the skin were randomly divided into three treatment groups: (i) cryosurgical treatment, (ii) intralesional immunotherapy with a live BCG vaccine, (iii) intralesional immunotherapy with a BCG cell wall preparation. Complete tumour regression was obtained in all 10 crysurgically treated horses, in 6 of 10 live BCG treated horses, and in 7 of 10 BCG cell wall treated horses. One live BCG and 2 BCG cell wall treated horses showed partial tumour regression of more than 50% of the tumour area. Eleven horses with sarcoid tumours were not eligible for random allocation in the trial because unfavourable site or size of the tumour precluded cryosurgical treatment. These animals were treated with BCG cell wall vaccine except for 1 animal, which was treated with live BCG. In 4 cases this treatment was combined with cytoreductive surgery of the tumour. In this prognostically unfavourable group 8 animals showed complete tumour regression and 3 animals did not respond.Regression after BCG immunotherapy appeared to correlate with size (larger tumours worse response) and localization of the sarcoid (less favourable results in the limb), and increase in peripheral blood leucocytes after the first injection. Horses with a positive delayed type hypersensitivity reaction to PPD before the start of treatment showed a tendency to more favourable prognosis than PPD negative horses. No correlation was present between regression and single or multiple presence of sarcoids, increase in body temperature after injection of BCG and the formation of specific antibodies to BCG. None of the cured animals have shown tumour recurrence 3 to 40 months following treatment.Animals were maintained under the guidelines prescribed by the Faculty of Veterinary Medicine, State University Utrecht, The NetherlandsGrant recipient of the Koningin Wilhelmina Fonds (Netherlands Cancer Foundation)     

Serum hormones and physical performance capacity in young boy athletes during a 1-year training period

Serum hormones and physical performance capacity in boy athletes (AG; n = 19) were investigated during a 1-year training period (between the ages of 11.6 and 12.6 years). Six young untrained boys served as the control group (CG). The mean serum testosterone concentration increased significantly in AG (P less than 0.05) following the training period from 2.92 nmol.l-1, SD 1.04 to 5.81 nmol.l-1, SD 1.33. Significant differences were not observed in the cortisol, sex hormone binding globulin and growth hormone levels during the follow-up period. The AG clearly increased speed (P less than 0.001), speed-strength (P less than 0.01-P less than 0.001) and anaerobic capacity (P less than 0.001) whereas CG had only slight increases (NS) in physical performance capacity during a 1-year period. During the last 6-month training period significant positive correlations (r = 0.49-0.58; P less than 0.05-P less than 0.01) were observed in AG between the relative changes in testosterone, testosterone:cortisol ratio and growth hormone and the relative performance change in speed, maximal isometric force and endurance, respectively. At the end of the period significant positive correlations were observed in all subjects between the level of testosterone and speed-strength (r = 0.52-0.64; P less than 0.01-P less than 0.001) and anaerobic capacity (r = 0.49; P less than 0.05). It was concluded that an increase in anabolic activity with the synchronous training already has positive effects on trainability and physical performance capacity at an early stage in puberty.     

Inbreeding in the Thoroughbred horse

Changes in the inbreeding coefficient, F, in the Thoroughbred horse over the past 45 years have been investigated by genotyping 467 Thoroughbred horses (born between 1961 and 2006) using the Illumina Equine SNP50 bead chip, which comprises 54,602 SNPs uniformly distributed across the equine genome. The Spearman rank correlation coefficient, r, between the year of birth and F was estimated. The results indicate that inbreeding in Thoroughbreds has increased over the past 40 years, with r = 0.24, P < 0.001 demonstrating that there is a highly significant, though relatively weak correlation between the year of birth and inbreeding coefficients. Interestingly, the majority of the increase in inbreeding is post-1996 and coincides with the introduction of stallions covering larger numbers of mares.     

Embryo yield and plasma progesterone profiles in superovulated dairy cows and heifers.

This study was conducted to compare the superovulatory (SOV) response of dairy cows (n=172) and heifers (n=172), with two SOV treatments started at the mid-luteal-phase of the estrus cycle. Donors were randomly treated either with equine chorionic gonadotrophin (eCG) plus neutra-eCG serum (eCG+N group, n=167) or follicle stimulating gonadotrophin (FSH-P group, n=177).No significant differences were observed among groups in the percentage of superovulatory responsive donors (SR donors; corpora lutea (CL) >/=2), the mean number of total ova, fertilized ova and viable embryos recovered. Cows yielded significantly less total ova and less fertilized ova (P<0.05) and tended to yield less viable embryos (P<0.06) than heifers.Plasma progesterone (P4) concentrations (n=135 donors) on the day of PGF(2alpha) (PGF) injection and on the day of SOV estrus were significantly higher (P<0.01) in eCG+N than in FSH-P donors and, the increase between those 2 days was also significantly higher (P<0.05) in group eCG+N than in group FSH-P, suggesting a higher luteotrophic effect of eCG than FSH-P. SR donors had P4 levels significantly higher (P<0.001) than non-SR donors only on day 5 after the SOV estrus and on the day of embryo recovery. Plasma P4 concentrations at 5 days after the SOV estrus and at embryo recovery correlated significantly (r=0.76, P<0.001).Heifers had significantly higher P4 levels than cows at gonadotrophin injection (P<0.01), PGF injection (P<0.001), 5 days (P<0.01) and 7 days (P<0.001) after the SOV estrus. At day 7 after the SOV estrus, P4 concentrations per ova recovered were significantly higher in heifers than in cows (P<0.01). The increase of plasma P4 per ova recovered, between days 5 and 7 after the SOV estrus, was significantly (P<0.01) higher in heifers than in cows. Also, the increase of plasma P4 between injections of gonadotrophin and PGF was significantly higher (P<0.05) in heifers than in cows.These results suggest that heifers have higher plasma P4 concentrations at diestrus (either before or after the SOV treatment) and this is associated with a higher embryo yield and quality, as compared to lactating cows. These higher plasma P4 concentrations reflect not only differences in ovulation rate as well as the competence of the corpus luteum, which is potentialized by gonadotrophin stimulation.     

Bluetongue virus serotype 8: abortion and transplacental transmission in cattle in the Burgundy region, France, 2008-2009

During the incursion of bluetongue virus (BTV) serotype 8 in France in 2007, an increase in the number of abortions in cattle was observed, but the cause was not clearly established. A survey of all the reported cases of abortion in cattle from November 2008 to April 2009 was conducted in the Nièvre district (Burgundy region) to determine the percentage of abortions as a result of BTV-8 and to study factors that could have played a role in BTV-8 transplacental transmission. BTV-8 was present in 16% of the fetuses or newborn calves that died within 48 h, from 780 dams. Dams inseminated before the BTV epizootic peak recorded from July to September 2008 were more likely to have BTV-positive abortions (OR=5.7, P<0.001) and those vaccinated in May or June 2008 were less likely to have BTV-positive abortions (OR=0.3, P=0.01 and OR=0.4, P=0.001, respectively). The gestational month was not a predictor of BTV abortion. In blood or spleen, fetuses/calves from RT-PCR-positive dams had significantly higher RNA concentrations than fetuses/calves from RT-PCR-negative dams. Of the 128 dams that had BTV-positive fetuses or calves, 60% were RT-PCR-negative. BTV-8-positive fetuses/calves were significantly more frequent (n=42 vs n=21, P=0.082) amongst those showing clinical signs or lesions suggestive of cerebral damage.     

Effects of smoking and obesity on the association between CDH13 (rs3865188) and adiponectin among Korean men: the KARE study

Adiponectin is secreted exclusively by adipocytes. Adiponectin is regulated by obesity, smoking, and genetic factors, including CDH13, which may contribute to development of diseases such as cardiovascular disease. Therefore, we aim to explore the joint effect of smoking and obesity on the association between CDH13 (rs3865188) and adiponectin among Korean men. This study included 1,570 Korean men aged 40-69 years who participated in the KARE cohort study (community-based cohorts, South Korea) from 2001. Hypoadiponectinemia was defined as the lowest quartile of adiponectin. In this study, individuals with at least one at-risk allele, the T allele, had an increased risk for hypoadiponectinemia, particularly current smokers with at least one T allele together with obesity when compared to those without the T allele. In addition, individuals with the TT genotype of CDH13 rs3865188, as well as obesity, were significantly associated with a 1.8-fold (odds ratio (OR) = 9.4, 95% confidence interval (CI) = 4.4-19.6, P < 0.001) increased risk for hypoadiponectinemia compared to individuals with the TT genotype of CDH 13 rs3865188 and normal waist circumference (WC) (OR = 5.1, 95% CI = 3.5-7.6, P < 0.001). However, in the joint effect of smoking and obesity, current smokers with the TT genotype of CDH13 rs3865188, as well as obesity, were significantly associated with a 6.2-fold (OR = 24.2, 95% CI = 3.0-196.6, P < 0.001) increased risk for hypoadiponectinemia compared to nonsmokers with the TT genotype of CDH 13 rs3865188 with normal WC (OR = 3.9, 95% CI = 1.7-9.3, P < 0.001). This study suggested that the association between CDH13 and adiponectin can be modified by lifestyle factors, such as smoking and obesity, among Korean men.     

Risk Factors for Poor Treatment Outcomes in Patients with MDR-TB and XDR-TB in China: Retrospective Multi-Center Investigation

Background

The treatment of patients with MDR- and XDR-TB is usually more complex, toxic and costly and less effective than treatment of other forms of TB. However, there is little information available on risk factors for poor outcomes in patients with MDR- and XDR-TB in China.

Methodology/Principal Findings

We retrospectively analyzed the clinical records of HIV-negative TB Patients with culture-proven MDR- or XDR-TB who were registered from July 2006 to June 2011 at five large-scale Tuberculosis Specialized Hospitals in China. Among 1662 HIV-seronegative TB cases which were culture-positive for M. tuberculosis complex and had positive sputum-smear microscopy results, 965 cases (58.1%) were DR-TB, and 586 cases (35.3%) were classified as having MDR-TB, accounting for 60.7% of DR-TB. 169 cases (10.2%) were XDR-TB, accounting for 17.5% of DR-TB, 28.8% of MDR-TB. The MDR-TB patients were divided into XDR-TB group (n=169) and other MDR-TB group (non-XDR MDR-TB) (n=417). In total, 240 patients (40.95%) had treatment success, and 346 (59.05%) had poor treatment outcomes. The treatment success rate in other MDR-TB group was 52.2%, significantly higher than that in the XDR-TB group (13%, P<0.001). In multivariate logistic regression analysis, poor outcomes were associated with duration of previous anti-TB treatment of more than one year (OR, 0.077; 95% CI, 0.011-0.499, P<0.001), a BMI less than 18.5 kg/m² (OR, 2.185; 95% CI, 1.372-3.478, P<0.001), XDR (OR, 13.368; 95% CI, 6.745-26.497, P<0.001), retreatment (OR, 0.171; 95% CI, 0.093-0.314, P<0.001), diabetes (OR, 0.305; 95% CI, 0.140-0.663, P=0.003), tumor (OR, 0.095; 95% CI, 0.011-0.795, P=0.03), decreased albumin (OR, 0.181; 95% CI, 0.118-0.295, P<0.001), cavitation (OR, 0.175; 95% CI, 0.108-0.286, P<0.001).

Conclusions/Significance

The patients with MDR-TB and XDR-TB have poor treatment outcomes in China.The presence of extensive drug resistance, low BMI, hypoalbuminemia, comorbidity, cavitary disease and previous anti-TB treatment are independent prognostic factors for poor outcome in patients with MDR-TB.     

IGF2 polymorphisms are associated with hepatitis B virus clearance and hepatocellular carcinoma

The aim of this study was to determine whether IGF2 polymorphisms are associated with the clearance of hepatitis B virus (HBV) infection and the risk of hepatocellular carcinoma (HCC). A total of 1095 Korean subjects were prospectively enrolled in this case-control study. The rates of IGF2 polymorphisms were determined in each group. The IGF2+820G allele (IGF2+820G/G) and the IGF2+6815A/A genotype were strongly associated with the resolution of HBV infection (OR=0.62-0.73; P=0.001-0.03 and OR=0.71; P=0.03, respectively). Haplotype analysis showed that IGF2-haplotype5 (A-C-C-T-A-T-G) and IGF2-haplotype1 (T-C-T-T-A-C-A) were significantly associated with the clearance and persistence of HBV infection (OR=0.55-0.58, P=0.009-0.01 and OR=1.31-1.65, P=0.001-0.007, respectively). On the other hand, the IGF2+2482C/C or +820G/G genotypes were significantly associated with a higher risk of HCC (OR=1.88, 1.68; P=0.04). IGF2 polymorphisms were found to be strongly associated with the clearance of HBV or the occurrence of HCC in patients with chronic HBV infection.     

Mitochondrial nt3010G-nt3970C haplotype is implicated in high-altitude adaptation of Tibetans

Tibetans are well adapted to living and thriving in high-altitude environments. Mitochondria are central links to oxygen consumption, and variations in mitochondrial DNA (mtDNA) could play a role in high-altitude adaptation. Alleles at several polymorphic sites in mtDNA define common haplotypes, or haplogroups, including some that have been implicated in the risk of developing certain diseases. However, few reports have determined whether relationships exist between haplogroups and high-altitude adaptation in the Tibetan population. The D4 haplogroup is a major haplogroup of the Han Chinese. In the present study, genotypes of 12 polymorphisms were determined in members of a Tibetan population (n = 72), low altitude-Han (la-Han, n = 144), and high altitude-Han (ha-Han, n = 227) populations using polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction-ligase detection reaction assays. The mitochondrial haplogroup D4 was negatively associated with high-altitude adaptation in Tibetans (P = 0.001 vs. la-Han, OR = 0.166, 95% CI = 0.048-0.567; P = 0.009 vs. ha-Han OR = 0.232, 95% CI = 0.069-0.778). The frequency of the nt3010G-nt3970C haplotype was significantly higher in Tibetans than in la-Han (P = 0.000) and ha-Han (P = 0.001) subjects. Findings in the present study suggest that unique mitochondrial variations determine a genetic background that is associated with high-altitude adaptation in the Tibetan population.