High resolution mapping of Y haplogroup G in Tyrol (Austria)

The distribution of Y-chromosomal haplogroup G2a (G-P15) in present-day paternal lineages in Tyrol (Austria) was analyzed by applying a high-density regional sampling scheme that also covered remote mountain areas. There is evidence from ancient genetic data for a high frequency of Y-chromosomal haplogroup G in prehistoric populations of Central Europe, whilst nowadays levels well below 10% are routinely observed. A population sample comprising ∼3700 specimens was analyzed for Y-chromosomal variation by genotyping Y-SNPs and Y-STRs. The set of binary markers included nine SNPs specific for sub-lineages of haplogroup G. The frequency of haplogroup G in 2379 unrelated men born in Tyrol amounted to 11.3%. Nearly all of these Y chromosomes belonged to haplogroup G2a. The main sub-haplogroup within G2a was defined by the SNP L497 (G2a3b1c) and reached a population frequency of 8.6%. Although this average level is higher than reported for other countries the geographical distribution of haplogroup G-L497 showed a differentiated pattern with a clustered distribution within some alpine valleys, where maxima above 40% were found. Both, the estimation of coalescent times and a principle coordinates analysis based on R_ST values derived from Y-STR haplotypes from different sub-regions of Tyrol revealed evidence for an old settlement history associated with Y chromosomes belonging to haplogroup G in the Tyrolean Alps.     

195例正常人右向左分流发生率及特点的 研究

【摘要】
目的 观察正常人不同年龄组右向左分流（right-to-left shunt，RLS）的发生率、分流量、分流类型，
以及比较两个年龄组RLS的特点。
方法 收集接受对比增强经颅多普勒超声（contrast-enhanced transcranial Doppler，cTCD）的正常人群
的临床资料。根据年龄将18～45岁纳入青年组，大于45岁纳入中年组。以肘前静脉注射激活的生理盐
水作为造影剂，结合Valsalva动作，行M模经颅多谱勒超声（power M-mode transcranial Doppler，mpTCD）
监测，诊断RLS并对分流量进行分级，分析不同分流量和分流类型（固有型和潜在型）在研究人群中
的分布特点。
结果 共195例正常人入组，RLS发生率为28.7%，其中小量分流39例（20%）。青年组RLS发生率为
28.9%（39/135），中年组RLS发生率为28.3%（17/60），两组RLS发生率及分流量分布差异无显著性，
且均以小量分流为主。固有型34例（60.7%），潜在型22例（39.3%）。青年组固有型25例（64.0%），潜
在型14例（35.9%）；中年组固有型9例（52.9%），潜在型8例（47.1%）。组间分流类型差异无显著性。
结论 本研究所选人群中RLS发生率约为28.7%，且以小量分流者居多，青年人与中年人RLS发生率、
分流量、分流类型无差异。     

Cycles,phase synchronization,and entrainment in single-species phytoplankton populations

Complex dynamics, such as population cycles, can arise when the individual members of a population become synchronized. However, it is an open question how readily and through which mechanisms synchronization-driven cycles can occur in unstructured microbial populations. In experimental chemostats we studied large populations (>10⁹ cells) of unicellular phytoplankton that displayed regular, inducible and reproducible population oscillations. Measurements of cell size distributions revealed that progression through the mitotic cycle was synchronized with the population cycles. A mathematical model that accounts for both the cell cycle and population-level processes suggests that cycles occur because individual cells become synchronized by interacting with one another through their common nutrient pool. An external perturbation by direct manipulation of the nutrient availability resulted in phase resetting, unmasking intrinsic oscillations and producing a transient collective cycle as the individuals gradually drift apart. Our study indicates a strong connection between complex within-cell processes and population dynamics, where synchronized cell cycles of unicellular phytoplankton provide sufficient population structure to cause small-amplitude oscillations at the population level.     

浙江省近年来流感病毒株的抗原性及人群免疫状况分析

目的 为了解1998－1999年浙江省分离的流感病毒株的抗原性以及杭州市区人群对各类流感病毒的体液免疫力。方法 我们采用常规大量半加敏双向血凝抑制（HI）试验检测相应毒株的交叉HI滴度并计算相应的抗原比。用微量半加敏HI试验检测人群流感HI抗体滴度。结果 浙江省近2年来共分离到12株流感病毒代表株，其中11株为甲3（H3N2）亚型，1株为乙型。A3／浙防／10／98毒株与A3／汉防／359／95、A3悉尼／5／97、A3／沪防／1／98毒株的抗原比分别为1．4、4．0和16．0；A3／浙防／7／99毒株与上述3种标准毒株的抗原比分别为22．6、2．0和1．4。B／浙防／31／99毒株与B／京防／172／97和B／深防／12／97毒株的单向HI滴度分别为≥10240和40。杭州市区人群各型流感HI抗体阳性率为62．4％－100．0％，GMT在11．67－275．49之间。提示，除A3／浙防／10／98毒株抗原性类似于A3／汉防/359/95外，其余甲3亚型毒株的抗原性均类似于A3／沪防／1／98病毒。B型毒株抗原性属于巴拿马类病毒。结论 杭州市区人群对甲3亚型和B型巴拿马类毒株普遍具有HI抗体免疫力。     

Orofacial pain in young adults and associated childhood and adulthood factors: results of the population study, Wales, United Kingdom

Abstract – Objectives: The aim of the study was to investigate the prevalence of orofacial pain (OFP) among young adults (30–31 years old) and to determine the effect of childhood and adulthood risk factors on the occurrence of OFP. Methods: Prospective cohort study to investigate dental and social effects of malocclusion and effectiveness of orthodontic treatment was conducted in Wales, United Kingdom. At 20‐year follow‐up 337 subjects aged 30–31 participated (74% from previous follow‐up aged 19–20 and 33% from the baseline) and were asked about OFP. Results: The prevalence of OFP was 23% (95% CI: 19%, 28%). Childhood factors, socio‐demographic, lifestyle, health behavior factors, history of orthodontic treatment and tooth wear were not associated with OFP. Participants with OFP were more likely to report that their teeth did not fit together properly [odds ratio (OR) = 12.4, 95% CI: 2.7–56.5) and reported previous trauma to the jaws (2.3; 1.3–4.2). Both diurnal and nocturnal teeth clenching and grinding were significantly associated with OFP (3.1; 1.4–7.1). Participants with frequent headaches had increased risk of having OFP (3.7; 1.6–8.4) while having reported 4–10 types of pain in other parts of the body other than the head, was associated with OR = 9.2 (3.7–23.0). An increased tendency to have OFP was seen in those individuals with higher levels of psychological distress (2.3; 1.4–3.9), high score on Life Event Inventory (2.6; 1.3–5.3), depressive symptoms (2.2; 1.2–4.0) and stress (2.2; 1.2–4.0). High self‐esteem associated with lower risk of OFP (0.5; 0.3–0.9). Conclusions: This study shows that OFP is frequently reported by young adults aged 30–31 and supports a multifactorial etiology with factors from many domains, including local mechanical factors, psychological and co‐morbidities. However, none of the childhood factors considered in this study were associated with OFP in adulthood.     

匹美西林治疗尿路感染的作用机制

近年来，我国尿路感染发病率和细菌耐药率呈逐年增加趋势，由于细菌耐药导致临床选择抗菌药物日益困难，尤其对特殊人群。匹美西林是一种新型的β-内酰胺类抗菌药物，对大肠埃希菌抗菌活性高，为单纯性尿路感染治疗的一线用药。匹美西林为美西林的前体药物，口服吸收后在体内迅速水解为美西林，与青霉素结合蛋白-2（PBP-2）结合，干扰细菌细胞壁生物合成，引起细菌形态改变使细胞溶解，从而发挥抗菌作用。匹美西林对革兰阴性菌活性强于革兰阳性菌，且对产超广谱β-内酰胺酶（ESBLs）大肠埃希菌有较强活性。该药在国外已上市数十年，安全有效，耐药率低，具有药物经济学优势。本文对尿路感染抗菌药物选择、匹美西林药效学和药动学、特殊人群用药以及安全性、经济性等方面进行了综述。     

Numerical validation and properties of a rapid binding approximation of a target-mediated drug disposition pharmacokinetic model

Target mediated drug disposition (TMDD) describes the phenomenon where high affinity binding of a drug to its pharmacological target (enzymes or receptors) significantly alters the pharmacokinetic profile of the drug. A rapid binding model replaces the often inestimable binding micro-constants (k _on and k _off) of TMDD models with the equilibrium dissociation constant (K _D) by assuming rapid binding of the drug to its target. The purpose of this study is to examine the validity of the rapid binding assumption and the pharmacokinetic properties of this model. Temporal profiles of free drug in plasma and a non-specific distribution site, free receptor, and the pharmacodynamically relevant, drug–receptor complex obtained from the rapid binding model compared favorably with the full TMDD model for small values of the parameter ɛ, which represents the ratio of the time required for drug–receptor binding relative to the time required for drug to be cleared from the system. The effect of escalating drug doses on the temporal characteristics and the comparison between the two models has been numerically investigated. A closer match between the full and rapid binding models is observed for high doses. Analysis for very large doses (Dose/V _c) relative to endogenous steady-state receptor concentration (R _ss), reveals that the rapid binding model reduces to a standard two compartmental model with a plasma compartment with linear drug elimination and a peripheral compartment. Decreasing clearance with increasing dose and decreasing R _ss indicates that for drugs exhibiting TMDD, the relative ratio of R _ss and dose is an important determinant of the pharmacokinetic properties rather than the individual parameters alone. An analytical solution derived for clearance shows that the primary elements of the apparent clearance of the drug are the linear clearance given by k _el V _c, the non-linear clearance due to drug–receptor complex internalization (k _int), and the ratio of AUC values of the receptor complex to that of free drug. Overall, simulations and analytical techniques applied here provide a better understanding of the validity of the rapid binding model and provide guidelines for its application. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.