Background—: A functional polymorphism in the inhibitory IgG-Fc receptor gene Fc γ RIIB influences intravenous immunoglobulin (IVIG) response in Kawasaki disease (KD), a vasculitis preferentially affecting the coronary arteries in children. We tested the hypothesis that the polymorphisms in the activating receptors ( Fc γ RIIA , Fc γ RIIIA , and Fc γ RIIIB ) also influence susceptibility, IVIG treatment response, and coronary artery disease in patients with KD. Methods and Results—: We genotyped polymorphisms in the activating Fc γ RIIA , Fc γ RIIIA , and Fc γ RIIIB using pyrosequencing in 443 patients with KD, including 266 trios and 150 single parent-child pairs, in northwest United States and genetically determined race with 155 ancestry informative markers. We used family-based association to test for transmission disequilibrium and further generated pseudosibling controls for comparisons with the cases. The Fc γ RIIA-131H variant showed an association with KD ( P =0.001) with an additive odds ratio (OR) of 1.51 (95% CI, 1.16–1.96; P =0.002) for the primary combined population, which persisted in both white ( P =0.04) and Asian ( P =0.01) subgroups and is consistent with the recent genome-wide association study. We also identified overtransmission of the Fc γ RIIIB neutrophil antigen 1 (NA1) variant among IVIG nonresponders ( P =0.0002) and specifically to white IVIG nonresponders ( P =0.007). ORs for overall and white nonresponders were 3.67 (95% CI, 1.75–7.66; P =0.0006) and 3.60 (95% CI, 1.34–9.70; P =0.01), respectively. Excess NA1 transmission also occurred in patients with KD with coronary artery disease (OR _additive , 2.13; 95% CI, 1.11–4.0; P =0.02). Conclusions—: A common variation in Fc γ RIIA is associated with increased KD susceptibility. The Fc γ RIIIB-NA1 variant, which confers higher affinity for IgG than the NA2 variant, is a determining factor for treatment response. These activating Fc γ R s play an important role in KD pathogenesis and the IVIG antiinflammatory mechanism.

To systematically appraise the existing published literature on cervical cancer screening utilization, and associated barriers and facilitators, in Nepal. Systematic literature review and meta-analysis. PubMed/MEDLINE, CINAHL, Scopus, Embase, and, Google Scholar were systematically searched using Preferred Reporting Items for Systematic Review and Meta-Analysis guideline. All quantitative and qualitative studies reporting cervical cancer screening (using the Pap smear test or visual inspection with acetic acid or human papillomavirus test) utilization, barriers, and facilitators for screening were identified. A meta-analysis was performed to estimate Nepal's pooled cervical cancer screening utilization proportion. The search yielded 97 records, of which 17 studies were included. Fifteen studies were quantitative and two were qualitative. Of the 17 studies, six were hospital-based and six were community-based. The pooled cervical cancer screening utilization proportion (using Pap smear test) among Nepalese women was 17% from the studies in the hospital settings, and 16% in the community. Six studies reported barriers to cervical cancer screening, of which four reported embarrassments related to the gynecological examination and a low level of knowledge on cervical cancer. Three (of four) studies reported health personnel, and two studies reported screening services-related facilitators for cervical cancer screening. Our review reported that cervical cancer screening utilization (16%) is more than four times lower than the national target (70%) in Nepal. Multiple barriers such as low levels of knowledge and embarrassment are associated with cervical cancer screening utilization. Health personnel's gender, counseling, and privacy of screening services were commonly reported facilitators. These findings could help to inform future research, and policy efforts to increase cervical cancer screening utilization in Nepal.

Background: Local ancestry in relation to clinical cardiovascular events ( CVEs ) among African Americans can provide insight into their genetic susceptibility to the disease. Methods and Results: We examined local European ancestry ( LEA ) association with CVEs among 3000 African Americans from the Atherosclerosis Risk in Communities Study ( ARIC ). We estimated LEA using L ocal A ncestry Inference in ad M ixed P opulations using L inkage D isequilibrium ( LAMP ‐ LD ) and examined its association with myocardial infarction, stroke, coronary heart disease and its composite and cardiovascular disease composite using logistic regression. Genome‐wide significance was achieved by 121 LEA regions in relation to myocardial infarction and 2 in relation to the cardiovascular disease composite. The LEA region downstream of 4q32.1 was significantly associated with 2 times higher odds of myocardial infarction ( P =1.45×10 ⁻⁶ ). The LEA region upstream of 6q11.1 was associated with 0.37 times lower odds of fatal coronary heart disease ( P =7.34×10 ⁻⁴ ), whereas the LEA region downstream of 21q21.1 was associated with 1.55 times higher odds of composite coronary heart disease ( P= 3.45×10 ⁻⁴ ). Association of LEA with stroke was observed in the region upstream of 6p22.3 with a 1.57 times higher odds of stroke ( P =9.69×10 ⁻⁴ ). Likewise, the LEA region on 4q32.3 was associated with a 1.53 times higher odds of composite cardiovascular disease ( P= 3.04×10 ⁻⁴ ). We also found 20 of the LEA regions at previously significant cardiovascular disease single‐nucleotide polymorphisms to be associated with CVE in our study. Conclusions: Future studies are needed to replicate and/or determine the causal variants driving our associations and explore clinical applications for those consistently associated with CVEs .

Knowledge and Awareness of Human Papillomavirus (HPV), Cervical Cancer and HPV Vaccine among Women in Two Distinct Nepali Communities HPV;HPV vaccine;cervical cancer;Nepal;rural communities; Background: This study assessed human papillomavirus (HPV), cervical cancer, and HPV vaccine knowledge and awareness among women in two sub-populations in Nepal - Khokana, a traditional Newari village in the Lalitpur District about eight kilometers south of Kathmandu, and Sanphebagar, a village development committee within Achham District in rural Far-Western Nepal. Methods: Study participants were recruited during health camps conducted by Nepal Fertility Care Center, a Nepali non-governmental organization. Experienced staff administered a Nepali language survey instrument that included questions on socio-demographics, reproductive health and knowledge on HPV, cervical cancer, and the HPV vaccine. Results: Of the 749 participants, 387 (51.7%) were from Khokana and 362 (48.3%) were from Sanphebagar. Overall, 53.3% (n=372) of women were aware of cervical cancer with a significant difference between Khokana and Sanphebagar (63.3% vs 43.0%; p=0.001). Overall, 15.4% (n=107) of women had heard of HPV and 32% (n=34) of these women reported having heard of the HPV vaccine. If freely available, 77.5% of the women reported willingness to have their children vaccinated against HPV. Factors associated with cervical cancer awareness included knowledge of HPV (Khokana: Odds Ratio (OR)=24.5; (95% Confidence Interval (CI): 3.1-190.2, Sanphebagar: OR=14.8; 95% CI: 3.7-58.4)) and sexually transmitted infections (Khokana: OR=6.18; 95% CI: 3.1-12.4; Sanphebagar: OR=17.0; 95% CI: 7.3-39.7) among other risk factors. Conclusions: Knowledge and awareness of HPV, cervical cancer, and the HPV vaccine remains low among women in Khokana and Sanphebagar. Acceptance of a freely available HPV vaccine for children was high, indicating potentially high uptake rates in these communities.