A comprehensive exploration of the genetic legacy and forensic features of Afghanistan and Pakistan Mongolian-descent Hazara

Afghanistan and Pakistan are rich with a complex landscape of culture, linguistics, ethnicity and genetic legacy at the crossroads between Indian-Subcontinent and Central Asia. Hazara people have historically been suggested to be Mongolian decedents but seldom been genetically studied. To dissect the genetic structure and explore the forensic characteristics of Hazara people, we first genotyped 30 Insertion/deletion (Indel) markers in 468 samples from 2 aboriginal Hazara populations from Afghanistan and Pakistan, and 100 East Asian comparative Bouyei samples using the Investigator® DIPplex kit. Subsequently, we carried out a comprehensive population genetic analysis from four different datasets: 8895 30-Indel genotype data from 51 populations, 15,895 30-Indel allele frequency data from 98 populations, 1048 genotypes of 993 STRs and Indels from 53 HGDP populations and 2068 whole-genomes (621,799 single nucleotide polymorphisms) from 165 worldwide Human origin reference populations, to further unravel the genetic complexity between Hazara and worldwide human populations using various statistical analysis. We find that 30 Indels are in accordance with HWE, and informative and polymorphic in both Central Asians Hazara and East Asian Bouyei populations. The forensic combined probability of exclusion is larger than 0.9943 and the cumulative power of discrimination is larger than 0.99999999999936. These forensic parameters show the high level of diversity, which makes the Indel amplification system suitable for forensic routine work and may be used as a supplementary assay for routine forensic investigation. The results from pairwise genetic distances, MDS, PCA, and phylogenetic relationship reconstruction demonstrate that present-day Hazaras are genetically closer to the Turkic-speaking populations (Uyghur, Kazakh, and Kyrgyz) residing in northwest China than with other Central/South Asian populations and Mongolian. Outgroup and admixture f_3, f₄, f₄-ratio, qpWave, and qpAdm results further demonstrate that Hazara shares more alleles with East Asians than with other Central Asians and carries 57.8% Mongolian-related ancestry. Overall, our findings suggest that Hazaras have experienced genetic admixture with the local or neighboring populations and formed the current East-West Eurasian admixed genetic profile after their separation from the Mongolians.     

Women's Use and Perceptions of Commercial Lubricants: Prevalence and Characteristics in a Nationally Representative Sample of American Adults

IntroductionUse of commercial lubricant is common in the United States among adult women. However, little is known about the sexual behaviors for which women use lubricant, women's perceptions of lubricant, or reasons for use, particularly in a nationally representative sample.AimThe aim of this study was to document the prevalence and characteristics of lubricant use among adult women in the United States and their perceptions of lubricants in relation to subjective sexual experiences.MethodsData are from a subset of individuals who were sampled as part of the 2012 National Survey of Sexual Health and Behavior, which involved the administration of an online questionnaire to a nationally representative probability sample of U.S. adults ages 18 and older.Main Outcome MeasuresSociodemographic characteristics, recent and lifetime commercial lubricant use, lubricant use during specific sexual behaviors, frequency of lubricant use, and reasons for lubricant use of participants were studied for the article.ResultsOf the women who participated in the study, 65.5% (n = 1,021) reported ever having used lubricant and 20% had used a lubricant within the past 30 days. Across age groups, lubricant was most commonly used during intercourse (58.3% of women) or partnered sexual play (49.6%). Common reasons for lubricant use included to make sex more comfortable, fun, and pleasurable and to decrease discomfort/pain.ConclusionsMost American women have used lubricant. Also, lubricant is more common as part of partnered intercourse and sexual play or foreplay compared with other solo and partnered sexual behaviors. Clinicians may find it helpful to broaden conversations with patients to include questions about their sexual behaviors, comfort and/or pain during sex, and lubricant use and to share, particularly with younger women, that lubricant use is prevalent and commonly used for reasons related to pleasure as well as comfort. Herbenick B, Reece M, Schick V, Sanders SA, and Fortenberry JD. Women's use and perceptions of commercial lubricants: Prevalence and characteristics in a nationally representative sample of American adults. J Sex Med 2014;11:642–652.     

Age estimation by the Cameriere’s normalized measurements (CNM) of the single permanent mandibular tooth on a panoramic radiograph

In this study Cameriere’s normalized measurements (CNM) of a single mandibular tooth were evaluated for age estimation on a sample of ortopantomographies (OPTs) of 2223 Italian children aged between 4 and 15 years.Dental maturity was radiographically evaluated by CNM of the seven left permanent mandibular teeth (CNMi = Ai/Li, i = 1,…,7); in monoradicular teeth, the distance (Ai, i = 1,…,5) between the inner sides of the open apex was measured while in biradicular teeth (Ai, i = 6, 7), the sum of the distances between the inner sides of the two open apices was calculated. Ai was normalized by the tooth length (Li, i = 1,…,7).The intra- and inter-observer agreement of CNM measurements was almost perfect. Overall, analyzed mandibular teeth finished their development up to the age of 13, but the distribution of CNM varied among different locations. The final models included a tooth-specific CNM as the independent variable and explained from 76% (second molars) to 39% (first incisors) of the variance in chronological age. The bias and accuracy of these models, when applied to real-life data with no age limitation, were within acceptable range of differences in the forensic anthropology of children. Specifically, in all models mean of absolute differences between estimated and real age was within one year (0.67 for first incisors to 1.00 for canines).In conclusion this study showed that all mandibular teeth do not have equal applicability for age estimation suggesting that further evaluation on different samples is necessary to evaluate the usefulness of a single mandibular tooth for age estimation.     

The self-assembling camptothecin-tocopherol prodrug: An effective approach for formulating camptothecin

Camptothecin (CPT) is a potent antitumor agent and functions via inhibiting the activity of topoisomerase I during DNA replication. However, the clinical application of CPT has been greatly hindered by its extremely poor solubility, the instability of its active lactone ring in blood stream, as well as the non-specific toxicity to normal tissues. In addition, most of the formulations developed so far are not applicable for formulating CPT. In this study, two novel CPT prodrugs were developed by conjugating CPT to α-tocopherol via a carbonate ester bond (CPT-VE) or disulfide linkage (CPT-S-S-VE). Both CPT prodrugs were able to self-assemble into nanofibers with the facilitation of a PEG_5K-Fmoc-VE₂-based nanomicellar carrier. Both prodrug nanoassemblies exhibited excellent stability. Fluorescence quenching, UV absorbance, and FT-IR studies demonstrated strong interactions between carrier and prodrugs, including hydrophobic interaction, π–π stacking, as well as hydrogen bonding. NMR studies suggested that prodrugs were successfully incorporated into PEG_5K-Fmoc-VE₂ during self-assembly process. In vitro, PEG_5K-Fmoc-VE₂/CPT-S-S-VE presented significantly higher level of cytotoxicity on tumor cells compared to PEG_5K-Fmoc-VE₂/CPT-VE. Biodistribution study showed that CPT-S-S-VE formulated in PEG_5K-Fmoc-VE₂ micelles was effectively converted to parent CPT following delivery to tumor tissues. Finally, PEG_5K-Fmoc-VE₂/CPT-S-S-VE nanofibers showed superior tumor growth inhibition in an aggressive murine breast cancer model (4T1.2).     

Comparative study on WHO Western Pacific Region and World Federation of Chinese Medicine Societies international standard terminologies on traditional medicine: Diseases of Gynecology and Obstetrics (Part 2)

<正>The following is the second discussion about how to understand and translate the names of diseases in traditional Chinese medicine(TCM)gynecology and obstetrics included in WHO International Standard Terminologies on Traditional Medicine in the Western Pacific Region(abbreviated as the WPRO Standard)[1]and the International Standard Chinese-English Basic Nomenclature of Chinese     

Comparative study on WHO Western Pacific Region and World Federation of Chinese Medicine Societies international standard terminologies on traditional medicine: Diseases of Gynecology and Obstetrics (Part 1)

<正>The diseases in traditional Chinese medicine(TCM)gynecology are usually related to menstruation,leucorrhea,pregnancy and psychology.About 69 terms are included in the WHO International Standard Terminologies on Traditional Medicine in the Western Pacific Region[1](abbreviated as the WPRO Standard)[1],and 177 in the International Standard Chinese-English Basic Nomenclature of Chinese     

Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder

BackgroundContactin-5 (CNTN5) is a candidate risk gene for autism spectrum disorder (ASD). Previous attempts to associate CNTN5 CNVs with ASD-susceptibility were limited by insufficient statistical power. Here, we aim to clarify the putative association between CNTN5 CNVs and ASD-risk using large-scale case-control analyses.MethodA CNTN5 CNV, shared by four brothers in a multiplex family with ASD, was initially identified. We calculated the prevalence and transmission of CNTN5 CNVs in cases across five ASD cohorts (n=15,784). Second, we compared the prevalence of CNTN5 CNVs in cases to their unaffected siblings (n=4,996). Third, we assessed the enrichment of CNTN5 CNVs in cases to extrafamilial controls across three cohorts (n=24,886) and the UK Biobank (n = 459,862). Finally, we evaluated the clinical impact of CNTN5 CNVs in a broad neurodevelopmental disorder cohort and the DECIPHER database.ResultsMost (96.7%) CNTN5 CNV deletions (0.193%) and duplications (0.03%) in cases were inherited by a parent that transmitted the variant to their affected and unaffected children at the same rate. We identified a significant enrichment of intronic CNTN5 CNV deletions in cases compared to extrafamilial controls (0.178% versus 0.019%; p-value=1.68E-05; OR:8.51; 95%CI=[2.58-44.21]). There was no difference in CNTN5 CNV enrichment between cases and individuals with NDDs.ConclusionsIntronic CNTN5 CNV deletions are rare, inherited, and intermediate effect size ASD-susceptibility variants that may also confer risk for other neuropsychiatric disorders. We offer a framework to characterize candidate variants that may not be detected through small-scale approaches to implicate intermediate effect size variants in the etiology of ASD.