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  1. Fulltext Prevalence of overweight/obesity among the medical students, Malaysia
    Gopalakrishnan S, Ganeshkumar P, Prakash MVS, Christopher, Amalraj V
    Med J Malaysia, 2012 Aug;67(4):442-4.
    PMID: 23082463
    BACKGROUND: Overweight and obesity are defined as abnormal or excessive fat accumulation that may impair health. Body mass index is a simple index of weight-for-height that is commonly used in classifying overweight and obesity in adult populations and individuals.
    OBJECTIVES: A study was conducted to screen the medical students of AIMST University for overweight/obesity using Body Mass Index(BMI) and to determine the prevalence among them.
    MATERIALS AND METHODS: This is an institution based cross sectional study was conducted among 290 medical students using a pre-tested questionnaire and measured their Body Mass Index (BMI). Data obtained was analyzed statistically by calculating proportions.
    RESULTS: Out of 290 students who participated in the study, 45.2% were males. In the study, 14.8% were found to be overweight (BMI 23-24.9 kg/m2); 13.7% of males and 15.7% of females. Pre-obese students (BMI 25-29kg/m2) accounted for 15.9% of the total (males 18.3% and females 13.8%). 5.2% were found to be obese (BMI > 30 kg/m2): males 9.2% and females 1.9%. Also 14.8% were found to be underweight (males 12.2% and females 17.0%). The study group consisted of 63.8% Indian, 32.4% Chinese and 3.8% Malay students.
    CONCLUSIONS: The study reveals that the prevalence of overweight and obesity among the medical students of AIMST University is on the high, which is comparable to the findings of earlier studies conducted in Malaysia, reinforcing the need to encourage healthy lifestyle, healthy food habits and a physically active daily routine, among the adolescents and youth of this country.
  2. The effectiveness of the McIsaac clinical decision rule in the management of sore throat: an evaluation from a pediatrics ward
    Thillaivanam S, Amin AM, Gopalakrishnan S, Ibrahim B
    Pediatr Res, 2016 Oct;80(4):516-20.
    PMID: 27331353 DOI: 10.1038/pr.2016.113
    BACKGROUND: Sore throats may be due to either viral or group A beta hemolytic streptococcus (GABHS) infections; but diagnosis of the etiology of a sore throat is difficult, often leading to unnecessary antibiotic prescriptions and consequent increases in bacterial resistance. Scoring symptoms using the McIsaac clinical decision rule can help physicians to diagnose and manage streptococcal infections leading to sore throat and have been recommended by the Ministry of Health, Malaysia. In this paper, we offer the first assessment of the effectiveness of the McIsaac rule in a clinical setting in Malaysia.

    METHOD: This study is a retrospective review of 116 pediatric patients presenting with sore throat. Group A comprised patients before the implementation of the McIsaac rule and Group B comprised patients after the implementation.

    RESULTS: Unnecessary throat swab cultures were reduced by 40% (P = 0.003). Redundant antibiotic prescriptions were reduced by 26.5% (P = 0.003) and the overall use of antibiotics was reduced by 22.1% (P = 0.003). The pediatricians' compliance rate to McIsaac rule criteria was 45% before implementation of the McIsaac rule, but improved to 67.9% (P = 0.0005) after implementation.

    DISCUSSION: The McIsaac rule is an effective tool for the management of sore throat in children in Malaysia.

  3. Fulltext Extended survival of Pleistocene Siberian wolves into the early 20th century on the island of Honshū
    Niemann J, Gopalakrishnan S, Yamaguchi N, Ramos-Madrigal J, Wales N, Gilbert MTP, et al.
    iScience, 2021 Jan 22;24(1):101904.
    PMID: 33364590 DOI: 10.1016/j.isci.2020.101904
    The Japanese or Honshū wolf was one the most distinct gray wolf subspecies due to its small stature and endemicity to the islands of Honshū, Shikoku, and Kyūshū. Long revered as a guardian of farmers and travellers, it was persecuted from the 17th century following a rabies epidemic, which led to its extinction in the early 20th century. To better understand its evolutionary history, we sequenced the nuclear genome of a 19th century Honshū wolf specimen to an average depth of coverage of 3.7✕. We find Honshū wolves were closely related to a lineage of Siberian wolves that were previously believed to have gone extinct in the Late Pleistocene, thereby extending the survival of this ancient lineage until the early 20th century. We also detected significant gene flow between Japanese dogs and the Honshū wolf, corroborating previous reports on Honshū wolf dog interbreeding.
  4. Fulltext Blue-Light-Blocking Lenses Ameliorate Structural Alterations in the Rodent Hippocampus
    Akansha EO, Bui BV, Ganeshrao SB, Bakthavatchalam P, Gopalakrishnan S, Mattam S, et al.
    Int J Environ Res Public Health, 2022 Oct 09;19(19).
    PMID: 36232222 DOI: 10.3390/ijerph191912922
    Evidence suggests that prolonged blue-light exposure can impact vision; however, less is known about its impact on non-visual higher-order functions in the brain, such as learning and memory. Blue-light-blocking lenses (BBLs) claim to reduce these potential impacts. Hence, we assessed structural and functional hippocampal alterations following blue-light exposure and the protective efficacy of BBLs. Male Wistar rats were divided into (n = 6 in each group) normal control (NC), blue-light exposure (LE), and blue-light with BBLs (Crizal Prevencia, CP and DuraVision Blue, DB) groups. After 28 days of light exposure (12:12 light: dark cycle), rats were trained for the Morris water maze memory retention test, and brain tissues were sectioned for hippocampal neuronal analysis using Golgi and Cresyl violet stains. The memory retention test was significantly delayed (p < 0.05) in LE compared with DB groups on day 1 of training. Comparison of Golgi-stained neurons showed significant structural alterations, particularly in the basal dendrites of hippocampal neurons in the LE group, with BBLs significantly mitigating these structural changes (p < 0.05). Comparison of Cresyl-violet-stained neurons revealed significantly (p < 0.001) increased degenerated hippocampal neurons in LE rats, with fewer degenerated neurons in the CP lens group for CA1 neurons (p < 0.05), and for both CP and DB groups (p < 0.05) for CA3 neurons. Thus, in addition to documented effects on visual centers, high-level blue-light exposure also results in degeneration in hippocampal neurons with associated behavioral deficits. These changes can be partially ameliorated with blue-light-blocking lenses.
  5. Evolutionary history of the extinct Sardinian dhole
    Ciucani MM, Jensen JK, Sinding MS, Smith O, Lucenti SB, Rosengren E, et al.
    Curr Biol, 2021 Dec 20;31(24):5571-5579.e6.
    PMID: 34655517 DOI: 10.1016/j.cub.2021.09.059
    The Sardinian dhole (Cynotherium sardous)1 was an iconic and unique canid species that was endemic to Sardinia and Corsica until it became extinct at the end of the Late Pleistocene.2-5 Given its peculiar dental morphology, small body size, and high level of endemism, several extant canids have been proposed as possible relatives of the Sardinian dhole, including the Asian dhole and African hunting dog ancestor.3,6-9 Morphometric analyses3,6,8-12 have failed to clarify the evolutionary relationship with other canids.We sequenced the genome of a ca-21,100-year-old Sardinian dhole in order to understand its genomic history and clarify its phylogenetic position. We found that it represents a separate taxon from all other living canids from Eurasia, Africa, and North America, and that the Sardinian dhole lineage diverged from the Asian dhole ca 885 ka. We additionally detected historical gene flow between the Sardinian and Asian dhole lineages, which ended approximately 500-300 ka, when the land bridge between Sardinia and mainland Italy was already broken, severing their population connectivity. Our sample showed low genome-wide diversity compared to other extant canids-probably a result of the long-term isolation-that could have contributed to the subsequent extinction of the Sardinian dhole.
  6. Historical population declines prompted significant genomic erosion in the northern and southern white rhinoceros (Ceratotherium simum)
    Sánchez-Barreiro F, Gopalakrishnan S, Ramos-Madrigal J, Westbury MV, de Manuel M, Margaryan A, et al.
    Mol Ecol, 2021 12;30(23):6355-6369.
    PMID: 34176179 DOI: 10.1111/mec.16043
    Large vertebrates are extremely sensitive to anthropogenic pressure, and their populations are declining fast. The white rhinoceros (Ceratotherium simum) is a paradigmatic case: this African megaherbivore has suffered a remarkable decline in the last 150 years due to human activities. Its subspecies, the northern (NWR) and the southern white rhinoceros (SWR), however, underwent opposite fates: the NWR vanished quickly, while the SWR recovered after the severe decline. Such demographic events are predicted to have an erosive effect at the genomic level, linked to the extirpation of diversity, and increased genetic drift and inbreeding. However, there is little empirical data available to directly reconstruct the subtleties of such processes in light of distinct demographic histories. Therefore, we generated a whole-genome, temporal data set consisting of 52 resequenced white rhinoceros genomes, representing both subspecies at two time windows: before and during/after the bottleneck. Our data reveal previously unknown population structure within both subspecies, as well as quantifiable genomic erosion. Genome-wide heterozygosity decreased significantly by 10% in the NWR and 36% in the SWR, and inbreeding coefficients rose significantly by 11% and 39%, respectively. Despite the remarkable loss of genomic diversity and recent inbreeding it suffered, the only surviving subspecies, the SWR, does not show a significant accumulation of genetic load compared to its historical counterpart. Our data provide empirical support for predictions about the genomic consequences of shrinking populations, and our findings have the potential to inform the conservation efforts of the remaining white rhinoceroses.
  7. Fulltext Genomes of Pleistocene Siberian Wolves Uncover Multiple Extinct Wolf Lineages
    Ramos-Madrigal J, Sinding MS, Carøe C, Mak SST, Niemann J, Samaniego Castruita JA, et al.
    Curr Biol, 2021 01 11;31(1):198-206.e8.
    PMID: 33125870 DOI: 10.1016/j.cub.2020.10.002
    Extant Canis lupus genetic diversity can be grouped into three phylogenetically distinct clades: Eurasian and American wolves and domestic dogs.1 Genetic studies have suggested these groups trace their origins to a wolf population that expanded during the last glacial maximum (LGM)1-3 and replaced local wolf populations.4 Moreover, ancient genomes from the Yana basin and the Taimyr peninsula provided evidence of at least one extinct wolf lineage that dwelled in Siberia during the Pleistocene.35 Previous studies have suggested that Pleistocene Siberian canids can be classified into two groups based on cranial morphology. Wolves in the first group are most similar to present-day populations, although those in the second group possess intermediate features between dogs and wolves.67 However, whether this morphological classification represents distinct genetic groups remains unknown. To investigate this question and the relationships between Pleistocene canids, present-day wolves, and dogs, we resequenced the genomes of four Pleistocene canids from Northeast Siberia dated between >50 and 14 ka old, including samples from the two morphological categories. We found these specimens cluster with the two previously sequenced Pleistocene wolves, which are genetically more similar to Eurasian wolves. Our results show that, though the four specimens represent extinct wolf lineages, they do not form a monophyletic group. Instead, each Pleistocene Siberian canid branched off the lineage that gave rise to present-day wolves and dogs. Finally, our results suggest the two previously described morphological groups could represent independent lineages similarly related to present-day wolves and dogs.
  8. Fulltext Interspecific Gene Flow Shaped the Evolution of the Genus Canis
    Gopalakrishnan S, Sinding MS, Ramos-Madrigal J, Niemann J, Samaniego Castruita JA, Vieira FG, et al.
    Curr Biol, 2018 11 05;28(21):3441-3449.e5.
    PMID: 30344120 DOI: 10.1016/j.cub.2018.08.041
    The evolutionary history of the wolf-like canids of the genus Canis has been heavily debated, especially regarding the number of distinct species and their relationships at the population and species level [1-6]. We assembled a dataset of 48 resequenced genomes spanning all members of the genus Canis except the black-backed and side-striped jackals, encompassing the global diversity of seven extant canid lineages. This includes eight new genomes, including the first resequenced Ethiopian wolf (Canis simensis), one dhole (Cuon alpinus), two East African hunting dogs (Lycaon pictus), two Eurasian golden jackals (Canis aureus), and two Middle Eastern gray wolves (Canis lupus). The relationships between the Ethiopian wolf, African golden wolf, and golden jackal were resolved. We highlight the role of interspecific hybridization in the evolution of this charismatic group. Specifically, we find gene flow between the ancestors of the dhole and African hunting dog and admixture between the gray wolf, coyote (Canis latrans), golden jackal, and African golden wolf. Additionally, we report gene flow from gray and Ethiopian wolves to the African golden wolf, suggesting that the African golden wolf originated through hybridization between these species. Finally, we hypothesize that coyotes and gray wolves carry genetic material derived from a "ghost" basal canid lineage.
  9. Fulltext Genomic Adaptations and Evolutionary History of the Extinct Scimitar-Toothed Cat, Homotherium latidens
    Barnett R, Westbury MV, Sandoval-Velasco M, Vieira FG, Jeon S, Zazula G, et al.
    Curr Biol, 2020 Dec 21;30(24):5018-5025.e5.
    PMID: 33065008 DOI: 10.1016/j.cub.2020.09.051
    Homotherium was a genus of large-bodied scimitar-toothed cats, morphologically distinct from any extant felid species, that went extinct at the end of the Pleistocene [1-4]. They possessed large, saber-form serrated canine teeth, powerful forelimbs, a sloping back, and an enlarged optic bulb, all of which were key characteristics for predation on Pleistocene megafauna [5]. Previous mitochondrial DNA phylogenies suggested that it was a highly divergent sister lineage to all extant cat species [6-8]. However, mitochondrial phylogenies can be misled by hybridization [9], incomplete lineage sorting (ILS), or sex-biased dispersal patterns [10], which might be especially relevant for Homotherium since widespread mito-nuclear discrepancies have been uncovered in modern cats [10]. To examine the evolutionary history of Homotherium, we generated a ∼7x nuclear genome and a ∼38x exome from H. latidens using shotgun and target-capture sequencing approaches. Phylogenetic analyses reveal Homotherium as highly divergent (∼22.5 Ma) from living cat species, with no detectable signs of gene flow. Comparative genomic analyses found signatures of positive selection in several genes, including those involved in vision, cognitive function, and energy consumption, putatively consistent with diurnal activity, well-developed social behavior, and cursorial hunting [5]. Finally, we uncover relatively high levels of genetic diversity, suggesting that Homotherium may have been more abundant than the limited fossil record suggests [3, 4, 11-14]. Our findings complement and extend previous inferences from both the fossil record and initial molecular studies, enhancing our understanding of the evolution and ecology of this remarkable lineage.
  10. Ancient DNA reveals genetic admixture in China during tiger evolution
    Sun X, Liu YC, Tiunov MP, Gimranov DO, Zhuang Y, Han Y, et al.
    Nat Ecol Evol, 2023 Nov;7(11):1914-1929.
    PMID: 37652999 DOI: 10.1038/s41559-023-02185-8
    The tiger (Panthera tigris) is a charismatic megafauna species that originated and diversified in Asia and probably experienced population contraction and expansion during the Pleistocene, resulting in low genetic diversity of modern tigers. However, little is known about patterns of genomic diversity in ancient populations. Here we generated whole-genome sequences from ancient or historical (100-10,000 yr old) specimens collected across mainland Asia, including a 10,600-yr-old Russian Far East specimen (RUSA21, 8× coverage) plus six ancient mitogenomes, 14 South China tigers (0.1-12×) and three Caspian tigers (4-8×). Admixture analysis showed that RUSA21 clustered within modern Northeast Asian phylogroups and partially derived from an extinct Late Pleistocene lineage. While some of the 8,000-10,000-yr-old Russian Far East mitogenomes are basal to all tigers, one 2,000-yr-old specimen resembles present Amur tigers. Phylogenomic analyses suggested that the Caspian tiger probably dispersed from an ancestral Northeast Asian population and experienced gene flow from southern Bengal tigers. Lastly, genome-wide monophyly supported the South China tiger as a distinct subspecies, albeit with mitochondrial paraphyly, hence resolving its longstanding taxonomic controversy. The distribution of mitochondrial haplogroups corroborated by biogeographical modelling suggested that Southwest China was a Late Pleistocene refugium for a relic basal lineage. As suitable habitat returned, admixture between divergent lineages of South China tigers took place in Eastern China, promoting the evolution of other northern subspecies. Altogether, our analysis of ancient genomes sheds light on the evolutionary history of tigers and supports the existence of nine modern subspecies.
  11. Fulltext The evolutionary history of extinct and living lions
    de Manuel M, Barnett R, Sandoval-Velasco M, Yamaguchi N, Garrett Vieira F, Zepeda Mendoza ML, et al.
    Proc Natl Acad Sci U S A, 2020 May 19;117(20):10927-10934.
    PMID: 32366643 DOI: 10.1073/pnas.1919423117
    Lions are one of the world's most iconic megafauna, yet little is known about their temporal and spatial demographic history and population differentiation. We analyzed a genomic dataset of 20 specimens: two ca. 30,000-y-old cave lions (Panthera leo spelaea), 12 historic lions (Panthera leo leo/Panthera leo melanochaita) that lived between the 15th and 20th centuries outside the current geographic distribution of lions, and 6 present-day lions from Africa and India. We found that cave and modern lions shared an ancestor ca. 500,000 y ago and that the 2 lineages likely did not hybridize following their divergence. Within modern lions, we found 2 main lineages that diverged ca. 70,000 y ago, with clear evidence of subsequent gene flow. Our data also reveal a nearly complete absence of genetic diversity within Indian lions, probably due to well-documented extremely low effective population sizes in the recent past. Our results contribute toward the understanding of the evolutionary history of lions and complement conservation efforts to protect the diversity of this vulnerable species.
  12. Fulltext Arctic-adapted dogs emerged at the Pleistocene-Holocene transition
    Sinding MS, Gopalakrishnan S, Ramos-Madrigal J, de Manuel M, Pitulko VV, Kuderna L, et al.
    Science, 2020 06 26;368(6498):1495-1499.
    PMID: 32587022 DOI: 10.1126/science.aaz8599
    Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.
  13. Fulltext The population genomic legacy of the second plague pandemic
    Gopalakrishnan S, Ebenesersdóttir SS, Lundstrøm IKC, Turner-Walker G, Moore KHS, Luisi P, et al.
    Curr Biol, 2022 Nov 07;32(21):4743-4751.e6.
    PMID: 36182700 DOI: 10.1016/j.cub.2022.09.023
    Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%-40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th-19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.
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