Partial Amniote Sex Chromosomal Linkage Homologies Shared on Snake W Sex Chromosomes Support the Ancestral Super-Sex Chromosome Evolution in Amniotes

Squamate reptile chromosome 2 (SR2) is thought to be an important remnant of an ancestral amniote super-sex chromosome, but a recent study showed that the Siamese cobra W sex chromosome is also a part of this larger ancestral chromosome. To confirm the existence of an ancestral amniote super-sex chromosome and understand the mechanisms of amniote sex chromosome evolution, chromosome maps of two snake species [Russell’s viper: Daboia russelii (DRU) and the common tiger snake: Notechis scutatus (NSC)] were constructed using bacterial artificial chromosomes (BACs) derived from chicken and zebra finch libraries containing amniote sex chromosomal linkages. Sixteen BACs were mapped on the W sex chromosome of DRU and/or NSC, suggesting that these BACs contained a common genomic region shared with the W sex chromosome of these snakes. Two of the sixteen BACs were co-localized to DRU2 and NSC2, corresponding to SR2. Prediction of genomic content from all BACs mapped on snake W sex chromosomes revealed a large proportion of long interspersed nuclear element (LINE) and short interspersed nuclear element (SINE) retrotransposons. These results led us to predict that amplification of LINE and SINE may have occurred on snake W chromosomes during evolution. Genome compartmentalization, such as transposon amplification, might be the key factor influencing chromosome structure and differentiation. Multiple sequence alignments of all BACs mapped on snake W sex chromosomes did not reveal common sequences. Our findings indicate that the SR2 and snake W sex chromosomes may have been part of a larger ancestral amniote super-sex chromosome, and support the view of sex chromosome evolution as a colorful myriad of situations and trajectories in which many diverse processes are in action

Chromosome map of the Siamese cobra: did partial synteny of sex chromosomes in the amniote represent “a hypothetical ancestral super-sex chromosome” or random distribution?

Background Unlike the chromosome constitution of most snakes (2n=36), the cobra karyotype shows a diploid chromosome number of 38 with a highly heterochromatic W chromosome and a large morphologically different chromosome 2. To investigate the process of sex chromosome differentiation and evolution between cobras, most snakes, and other amniotes, we constructed a chromosome map of the Siamese cobra (Naja kaouthia) with 43 bacterial artificial chromosomes (BACs) derived from the chicken and zebra finch libraries using the fluorescence in situ hybridization (FISH) technique, and compared it with those of the chicken, the zebra finch, and other amniotes. Results We produced a detailed chromosome map of the Siamese cobra genome, focusing on chromosome 2 and sex chromosomes. Synteny of the Siamese cobra chromosome 2 (NKA2) and NKAZ were highly conserved among snakes and other squamate reptiles, except for intrachromosomal rearrangements occurring in NKA2. Interestingly, twelve BACs that had partial homology with sex chromosomes of several amniotes were mapped on the heterochromatic NKAW as hybridization signals such as repeat sequences. Sequence analysis showed that most of these BACs contained high proportions of transposable elements. In addition, hybridization signals of telomeric repeat (TTAGGG)n and six microsatellite repeat motifs ((AAGG)8, (AGAT)8, (AAAC)8, (ACAG)8, (AATC)8, and (AAAAT)6) were observed on NKAW, and most of these were also found on other amniote sex chromosomes. Conclusions The frequent amplification of repeats might involve heterochromatinization and promote sex chromosome differentiation in the Siamese cobra W sex chromosome. Repeat sequences are also shared among amniote sex chromosomes, which supports the hypothesis of an ancestral super-sex chromosome with overlaps of partial syntenies. Alternatively, amplification of microsatellite repeat motifs could have occurred independently in each lineage, representing convergent sex chromosomal differentiation among amniote sex chromosomes

Clinical risk-scoring algorithm to forecast scrub typhus severity

Pamornsri Sriwongpan,1,2 Pornsuda Krittigamas,3 Hutsaya Tantipong,4 Jayanton Patumanond,5 Chamaiporn Tawichasri,6 Sirianong Namwongprom1,71Clinical Epidemiology Program, Chiang Mai University, Chiang Mai, Thailand; 2Department of Social Medicine, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; 3Department of General Pediatrics, Nakornping Hospital, Chiang Mai, Thailand; 4Department of Medicine, Chonburi Hospital, Chonburi, Thailand; 5Clinical Epidemiology Program, Thammasat University, Bangkok, Thailand; 6Clinical Epidemiology Society at Chiang Mai, Chiang Mai, Thailand; 7Department of Radiology, Chiang Mai University, Chiang Mai, ThailandPurpose: To develop a simple risk-scoring system to forecast scrub typhus severity.Patients and methods: Seven years' retrospective data of patients diagnosed with scrub typhus from two university-affiliated hospitals in the north of Thailand were analyzed. Patients were categorized into three severity groups: nonsevere, severe, and dead. Predictors for severity were analyzed under multivariable ordinal continuation ratio logistic regression. Significant coefficients were transformed into item score and summed to total scores.Results: Predictors of scrub typhus severity were age >15 years, (odds ratio [OR] =4.09), pulse rate >100/minute (OR 3.19), crepitation (OR 2.97), serum aspartate aminotransferase >160 IU/L (OR 2.89), serum albumin ≤3.0 g/dL (OR 4.69), and serum creatinine >1.4 mg/dL (OR 8.19). The scores which ranged from 0 to 16, classified patients into three risk levels: non-severe (score ≤5, n=278, 52.8%), severe (score 6–9, n=143, 27.2%), and fatal (score ≥10, n=105, 20.0%). Exact severity classification was obtained in 68.3% of cases. Underestimations of 5.9% and overestimations of 25.8% were clinically acceptable.Conclusion: The derived scrub typhus severity score classified patients into their severity levels with high levels of prediction, with clinically acceptable under- and overestimations. This classification may assist clinicians in patient prognostication, investigation, and management. The scoring algorithm should be validated by independent data before adoption into routine clinical practice.Keywords: severe scrub typhus, risk-scoring system, clinical prediction rule, prognostic predictor

Validation of a clinical risk-scoring algorithm for severe scrub typhus

Pamornsri Sriwongpan,1,2 Jayanton Patumanond,3 Pornsuda Krittigamas,4 Hutsaya Tantipong,5 Chamaiporn Tawichasri,6 Sirianong Namwongprom1,7 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, 2Department of Social Medicine, Chiangrai Prachanukroh Hospital, Chiang Rai, 3Clinical Epidemiology Program, Faculty of Medicine, Thammasat University, Bangkok, 4Department of General Pediatrics, Nakornping Hospital, Chiang Mai, 5Department of Medicine, Chonburi Hospital, Chonburi, 6Clinical Epidemiology Society at Chiang Mai, Chiang Mai, 7Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Objective: The aim of the study reported here was to validate the risk-scoring algorithm for prognostication of scrub typhus severity. Methods: The risk-scoring algorithm for prognostication of scrub typhus severity developed earlier from two general hospitals in Thailand was validated using an independent dataset of scrub typhus patients in one of the hospitals from a few years later. The predictive performances of the two datasets were compared by analysis of the area under the receiver-operating characteristic curve (AuROC). Classification of patients into non-severe, severe, and fatal cases was also compared. Results: The proportions of non-severe, severe, and fatal patients by operational definition were similar between the development and validation datasets. Patient, clinical, and laboratory profiles were also similar. Scores were similar in both datasets, both in terms of discriminating non-severe from severe and fatal patients (AuROC =88.74% versus 91.48%, P=0.324), and in discriminating fatal from severe and non-severe patients (AuROC =88.66% versus 91.22%, P=0.407). Over- and under-estimations were similar and were clinically acceptable. Conclusion: The previously developed risk-scoring algorithm for prognostication of scrub typhus severity performed similarly with the validation data and the first dataset. The scoring algorithm may help in the prognostication of patients according to their severity in routine clinical practice. Clinicians may use this scoring system to help make decisions about more intensive investigations and appropriate treatments. Keywords: severity, clinical prediction rule, algorithm, prognosis, Thailan

Effect of acetylsalicylic acid on thalassemia with pulmonary arterial hypertension

Nonlawan Chueamuangphan,1,2 Wattana Wongtheptian,2 Jayanton Patumanond,3 Apichard Sukonthasarn,4 Suporn Chuncharunee,5 Chamaiporn Tawichasri,6 Weerasak Nawarawong4 1Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Medicine, Chiang Rai Hospital, Chiang Rai, Thailand; 3Clinical Epidemiology Program, Faculty of Medicine, Thammasat University, Bangkok, Thailand; 4Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 5Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Clinical Epidemiology Society at Chiang Mai, Chiang Mai, Thailand Objective: To compare pulmonary artery systolic pressure (PASP) between thalassemic patients with pulmonary arterial hypertension (PAH) for whom acetylsalicylic acid (ASA) was and was not prescribed after 1 year. Methods: A retrospective cohort study was conducted at the hematological outpatient clinic at Chiang Rai Hospital, Chiang Rai, Thailand. All new cases of thalassemia with PAH from January 2007 to January 2012 were studied at the first month and at 12 months. The patients were classified into two groups. In one group, ASA 81 mg daily was prescribed for 1 year, whereas in another group no ASA was prescribed, due to its contraindications, which included bleeding, gastrointestinal side effects, and thrombocytopenia. PASP, estimated by a Doppler echocardiography, was measured by the same cardiologist. Propensity score adjustment was used to control confounding variables by indication and contraindication. Multivariable regression analysis was used to evaluate the effects of ASA. Results: Of the 63 thalassemia patients with PAH, there were 47 (74.6%) in the ASA group and 16 (25.4%) in the no ASA group. ASA, as compared with no ASA, did not significantly reduce PASP (adjusted difference -0.95; 95% confidence interval -16.99 to 15.10; P=0.906). Conclusion: Low-dose ASA may not have a beneficial effect on PASP after 1 year of treatment of PAH in thalassemia. Keywords: thalassemia, pulmonary arterial hypertension, acetylsalicylic aci

Take one step backward to move forward: Assessment of genetic diversity and population structure of captive Asian woolly-necked storks (Ciconia episcopus).

The fragmentation of habitats and hunting have impacted the Asian woolly-necked stork (Ciconia episcopus), leading to a serious risk of extinction in Thailand. Programs of active captive breeding, together with careful genetic monitoring, can play an important role in facilitating the creation of source populations with genetic variability to aid the recovery of endangered species. Here, the genetic diversity and population structure of 86 Asian woolly-necked storks from three captive breeding programs [Khao Kheow Open Zoo (KKOZ) comprising 68 individuals, Nakhon Ratchasima Zoo (NRZ) comprising 16 individuals, and Dusit Zoo (DSZ) comprising 2 individuals] were analyzed using 13 microsatellite loci, to aid effective conservation management. Inbreeding and an extremely low effective population size (Ne) were found in the KKOZ population, suggesting that deleterious genetic issues had resulted from multiple generations held in captivity. By contrast, a recent demographic bottleneck was observed in the population at NRZ, where the ratio of Ne to abundance (N) was greater than 1. Clustering analysis also showed that one subdivision of the KKOZ population shared allelic variability with the NRZ population. This suggests that genetic drift, with a possible recent and mixed origin, occurred in the initial NRZ population, indicating historical transfer between captivities. These captive stork populations require improved genetic variability and a greater population size, which could be achieved by choosing low-related individuals for future transfers to increase the adaptive potential of reintroduced populations. Forward-in-time simulations such as those described herein constitute the first step in establishing an appropriate source population using a scientifically managed perspective for an in situ and ex situ conservation program in Thailand