METHODS: To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716).
RESULTS: Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73-0.89, P = 1.49 × 10-5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10-5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47-0.81, P = 4.37 × 10-4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10-2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10-4) and Taiwan datasets (P = 2.99 × 10-2).
CONCLUSION: Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.
Methods: We systematically searched PubMed, EMBASE and Web of Science for studies published from their starting dates to Aug 7, 2018. The sex-specific hazard ratios (HRs) and their pooled ratio (women vs men) of all-cause and CHD mortality associated with type 2 diabetes were obtained through an inverse variance-weighted random-effects meta-analysis. Subgroup analyses were used to explore the potential sources of heterogeneity.
Results: The 35 analyzed prospective cohort studies included 2 314 292 individuals, among whom 254 038 all-cause deaths occurred. The pooled women vs men ratio of the HRs for all-cause and CHD mortality were 1.17 (95% CI: 1.12-1.23, I2 = 81.6%) and 1.97 (95% CI: 1.49-2.61, I2 = 86.4%), respectively. The pooled estimate of the HR for all-cause mortality was approximately 1.30 in articles in which the duration of follow-up was longer than 10 years and 1.10 in articles in which the duration of follow-up was less than 10 years. The pooled HRs for all-cause mortality in patients with type 2 diabetes was 2.33 (95% CI: 2.02-2.69) in women and 1.91 (95% CI: 1.72-2.12) in men, compared with their healthy counterparts.
Conclusions: The effect of diabetes on all-cause and CHD mortality is approximately 17 and 97% greater, respectively, for women than for men.
Method: Participants of this cross-sectional study included 99 full-term neonates (165 ears) with mean chronological age of 46.7 hrs (SD = 26.3 hrs). Of the 99 neonates, 58 were Malay, 28 were Indian, and 13 were Chinese. The neonates who passed high-frequency (1 kHz) tympanometry, acoustic stapedial reflex, and distortion product otoacoustic emission screening tests were assessed using a pressurized WBA test (wideband tympanometry). To reduce the number of measurement points, the WBA responses were averaged to 16 one-third octave frequency bands from 0.25 to 8 kHz. A mixed-model analysis of variance was applied to the data to investigate the effects of frequency, ear, gender, and ethnicity on WBA. The analysis of variance was also used to compare between WBA measured at TPP and 0 daPa. An interclass correlation coefficient test was applied at each of the 16 frequency bands to measure the test-retest reliability of WBA at TPP and 0 daPa.
Results: Both WBA measurements at TPP and 0 daPa exhibited a multipeaked pattern with 2 maxima at 1.25-1.6 kHz and 6.3 kHz and 2 minima at 0.5 and 4 kHz. The mean WBA measured at TPP was significantly higher than that measured at 0 daPa at 0.25, 0.4, 0.5, 1.25, and 1.6 kHz only. A normative data set was developed for absorbance at TPP and at 0 daPa. There was no significant effect of ethnicity, gender, and ear on both measurements of WBA. The test-retest reliability of WBA at TPP and 0 daPa was high with the interclass correlation coefficient ranging from 0.77 to 0.97 across the frequencies.
Conclusions: Normative data of WBA measured at TPP and 0 daPa for neonates were provided in the present study. Although WBA at TPP was slightly higher than the WBA measured at 0 daPa at some frequencies below 2 kHz, the WBA patterns of the 2 measurements were nearly identical. Moreover, the test-retest reliability of both WBA measurements was high.
METHODS: Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h and 30 min before the last dose were administered vehicle (control groups), 250 mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg ibuprofen (study groups), euthanized 6 h post last administration and sunitinib plasma, liver, kidney, brain concentrations analyzed.
RESULTS: Ibuprofen halved sunitinib plasma concentration in female mice (p