The Economic Burden of Cancers on Indian Households

We assessed the burden of cancer on households’ out-of-pocket health spending, non-medical consumption, workforce participation, and debt and asset sales using data from a nationally representative health and morbidity survey in India for 2004 of nearly 74 thousand households. Propensity scores were used to match households containing a member diagnosed with cancer (i.e. cancer-affected households) to households with similar socioeconomic and demographic characteristics (controls). Our estimates are based on data from 1,645 households chosen through matching. Cancer-affected households experienced higher levels of outpatient visits and hospital admissions and increased out-of-pocket health expenditures per member, relative to controls. Cancer-affected households spent between Indian Rupees (INR) 66 and INR 85 more per member on healthcare over a 15-day reference period, than controls and additional expenditures (per member) incurred on inpatient care by cancer-affected households annually is equivalent to 36% to 44% of annual household expenditures of matched controls. Members without cancer in cancer-affected households used less health-care and spent less on healthcare. Overall, adult workforce participation rates were lower by between 2.4 and 3.2 percentage points compared to controls; whereas workforce participation rates among adult members without cancer were higher than in control households. Cancer-affected households also had significantly higher rates of borrowing and asset sales for financing outpatient care that were 3.3% to 4.0% higher compared to control households; and even higher for inpatient care.     

Second Cancers in Patients with Neuroendocrine Tumors

Background

Second cancers have been reported to occur in 10-20% of patients with neuroendocrine tumors (NETs). However, most published studies used data from a single institution or focused only on specific sites of NETs. In addition, most of these studies included second cancers diagnosed concurrently with NETs, making it difficult to assess the temporality and determine the exact incidence of second cancers. In this nationwide population-based study, we used data recorded by the Taiwan Cancer Registry (TCR) to analyze the incidence and distribution of second cancers after the diagnosis of NETs.

Methods

NET cases diagnosed from January 1, 1996 to December 31, 2006 were identified from the TCR. The data on the occurrence of second cancers were ascertained up to December 31, 2008. Standardized incidence ratios (SIRs) of second cancers were calculated based on the cancer incidence rates of the general population. Cox-proportional hazards regression analysis was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of second cancers associated with sex, age, and primary NET sites.

Results

A total of 1,350 newly diagnosed NET cases were identified according to the selection criteria. Among the 1,350 NET patients, 49 (3.63%) developed a second cancer >3 months after the diagnosis of NET. The risk of second cancer following NETs was increased compared to the general population (SIR = 1.48, 95% CI: 1.09-1.96), especially among those diagnosed at age 70 or older (HR = 5.08, 95% CI = 1.69-15.22). There appeared to be no preference of second cancer type according to the primary sites of NETs.

Conclusions

Our study showed that the risk of second cancer following NETs is increased, especially among those diagnosed at age 70 or older. Close monitoring for the occurrence of second cancers after the diagnosis of NETs is warranted.     

Differential Expression of HPV16 L2 Gene in Cervical Cancers Harboring Episomal HPV16 Genomes: Influence of Synonymous and Non-Coding Region Variations

We tested the hypothesis that (i) synonymous variations within the coding regions, and (ii) variations within the non-coding regions of HPV, influence cervical cancer (CaCx) pathogenesis under the impact of intact HPV16 genomes. Whole genome sequence analysis of HPV16 isolates within 70 CaCx cases and 25 non-malignant samples revealed that synonymous variations were significantly higher within the E6 (p = 0.014), E5 (p = 0.001) and L2 (p = 0.0002) genes of HPV16 isolates within cases, compared to isolates within non-malignant samples. All of the 25 (100%) humanized codons identified within L2 ORF of the samples analyzed, were harbored by CaCx cases, while 8 out of 25 (32%) were harbored by HPV16 positive non-malignant samples (p = 3.87105E-07). L2 (mRNA and protein) expression was evident only among cases with episomal viral genomes and L2 mRNA expression correlated significantly with E2 gene copy numbers suggesting expression from all episomal genomes. Among such cases, Asian American (AA) isolates portrayed all of the humanized codons (100%; 4–6/sample) recorded within L2, which was significantly higher (p = 2.02E-7) compared to the European (E) isolates (22.8%; none or 1–2/sample). Additionally, majority of E variant isolates within cases (54/57; 94.7%) portrayed a variation (T4228C) within the short non-coding region (NCR2) between E5 and L2 genes, which portrays a weak promoter activity specific for L2 mRNA expression. This resulted in loss of 9 out of 14 miRNA binding sites (hsa-miR-548 family), despite the significant overexpression of miR548a-5p and miR548d-5p among such cases (28.64 and 36.25 folds, respectively), in comparison to HPV negative control samples. The findings exemplify the biological relevance of sequence variations in HPV16 genomes and highlight that episomal HPV16 in CaCx cases employ multiple mechanisms to sustain L2 expression, thereby justifying the potential role of L2 in such cancers, as opposed to those harboring viral integration.     

不定胚再生植株的染色体数目变异

本实验以甜瓜“小麦瓜”和“青皮绿肉”品种为试材,经不定胚诱导再生植株。分别调查了不同继代培养时间后形成再生植株的染色体数目,并将之与对照染色体数目相比较,发现通过诱导不定胚所得到的再生植株中存在着一定的变异,而且经过不同继代培养时间后,所得到的不定胚再生植株的变异程度不同,随着时间的增加,染色体数目的变异率从3.3%增加到30%,变异幅度也从2n=23~24增加到2n=13~48。从而得出结论：不定胚再生植株染色体数目变异程度随着培养时间的增加而增加;培养时间在1~2个月内所得到的不定胚再生植株的变异较少。此外,不定胚再生植株的染色体数目变异程度也因品种而异。 Abstract:Chromosomal number of different of somatic embryos regenerated plants were investigated in melon variety “xiaomaigua” and “Qingpilurou”.Certain variations of chromosomal number were found among the regenerated plants compared with normal sample,and range of variation covered from 2n=23～24 to 2n=13～48 with the increase of generation,the rate from 3.3% to 30%.The results indicated that degree of variation in chromosomal number of somatic embryos regenerated melon plants increased with the time of culture,and those cultured in one to two months had the least variation.It was also found that degree of chromosomal number variations varied with melon varieties.     

Identification of Promotor and Exonic Variations,and Functional Characterization of a Splice Site Mutation in Indian Patients with Unconjugated Hyperbilirubinemia

Background

Mild unconjugated hyperbilirubinemia (UH), due to reduced activity of the enzyme uridine diphosphoglucuronate-glucuronosyltransferase family, polypeptide 1 (UGT1A1), is a common clinical condition. Most cases are caused by presence in homozygous form of an A(TA)₇TAA nucleotide sequence instead of the usual A(TA)₆TAA sequence in promoter region of the UGT1A1 gene. In some cases, other genetic variations have been identified which differ between populations. There is need for more data on such genetic variations from India.

Methods

DNA from subjects with unexplained persistent or recurrent UH was tested for the presence of TA promoter insertions. In addition, all five exons and splicing site regions of UGT1A1 gene were sequenced. Several bioinformatics tools were used to determine the biological significance of the observed genetic changes. Functional analysis was done to look for effect of a splice site mutation in UGT1A1.

Results

Of 71 subjects with UH (68 male; median age [range], 26 [16–63] years; serum bilirubin 56 [26–219] μM/L, predominantly unconjugated) studied, 65 (91.5%) subjects were homozygous for A(TA)₇TAA allele, five (7.0%) were heterozygous, and one (1.4%) lacked this change. Fifteen subjects with UH had missense exonic single nucleotide changes (14 heterozygous, 1 homozygous), including one subject with a novel nucleotide change (p.Thr205Asn). Bioinformatics tools predicted some of these variations (p.Arg108Cys, p.Ile159Thr and p.Glu463Val) to be deleterious. Functional characterization of an exonic variation (c.1084G>A) located at a splice site revealed that it results in frameshift deletion of 31 nucleotides and premature truncation of the protein.

Conclusion

Our study revealed several single nucleotide variations in UGT1A1 gene in Indian subjects with UH. Functional characterization of a splice site variation indicated that it leads to disordered splicing. These variations may explain UH in subjects who lacked homozygous A(TA)₇TAA promoter alleles.     

人体颈椎松质骨显微结构和力学性能的区域性差异研究

目的:探讨人体脊柱松质骨骨骼显微结构和力学性能的区域性差异,为松质骨三维结构采样部位的选取提供参考。方法:显微CT扫描6块颈6椎体标本获得三维图像,依据椎体内解剖位置的不同,将松质骨划分为6个位置组:外侧、内侧、腹侧、背侧、头侧和尾侧。利用显微结构参数骨体积分数(Bone volume to tissue volume,BV/TV)、骨表面积和骨体积的比值(Bone surface to bone volume,BS/BV)、骨小梁数量(Trabecular number,Tb.N)、骨小梁厚度(Trabecular thickness,Tb.Th)、骨小梁分离度(Trabecular separation,Tb.Sp)和个体化骨小梁分割方法(Individual trabeculae segmentation,ITS)分析6个位置组内松质骨显微结构,并利用有限元分析,获得6个位置组内松质骨的力学性能参数表观弹性模量和表观剪切模量。分别两两对比外侧和内侧,腹侧和背侧,头侧和尾侧松质骨的显微结构参数(BV/TV、BS/BV、Tb.N、Tb.Th、Tb.Sp和个体化骨小梁分割得到的参数)和力学性能参数(表观弹性模量和表观剪切模量)。结果:头侧和尾侧的主要显微结构参数BV/TV、Tb.Th、Tb.N等和表观弹性模量均存在显著差异(P0.05)。腹侧和背侧、内侧和外侧的主要显微结构参数BV/TV、Tb.Th、Tb.N等无显著差异。外侧和内侧的表观弹性模量在非主方向即内外方向和腹背放上上存在显著差异(P0.05),在主方向即头尾上无显著差异。结论:在实验中采集椎体松质骨样本以及临床上利用高分辨率CT分析椎体松质骨结构时,感兴趣区域要同时涵盖头侧和尾侧。     

Multi-Purpose Utility of Circulating Plasma DNA Testing in Patients with Advanced Cancers

Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5–1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical ‘hot-spot’ mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid biomarker studies have clinically important multi-purpose utility in advanced cancer patients and further studies to pursue their incorporation into the standard of care are warranted.     

Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese Patients

BackgroundThe incidence of well-differentiated thyroid cancer (WDTC) is increasing rapidly. Many authors feel that this increase is due to over-diagnosis and that one of the contributing factors is the increasing use of various imaging studies. The rate of obesity has also been increasing in the United States. It has been suggested that patients with an increased body mass index (BMI kg/m²) have a higher incidence of WDTC than patients with normal BMI. One might hypothesize that thyroid nodules are more difficult to palpate in obese patients and that as more cancers are detected by imaging the apparent rate of increase in WDTC in obese patients would appear to be greater than in non-obese patients. This study was undertaken to evaluate this hypothesis by determining if there is any difference in the way thyroid cancers are initially detected in obese and non-obese patients.MethodsThe medical records of all 519 patients with a postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone Medical Center from January 1, 2007 through August 31, 2010 by the three members of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non-obese (BMI<30 kg/m²) and Obese (BMI≥30 kg/m²) groups. Patients were also divided by the initial method of detection of their tumor into Palpation, Imaging, and Incidental groups.ResultsThe final study group contained 270 patients, 181(67%) of whom were in the Non-obese Group and 89(33%) were in the Obese Group. In the Non-obese group, 81(45%) of tumors were found by palpation, 72(40%) were found by imaging, and 28(16%) were found incidentally. In the Obese group, 40(45%) were found by palpation, 38(43%) were found by imaging, and 11(12%) were found incidentally. These differences were not statistically significant (p-value 0.769).ConclusionWe show that BMI does not play a role in the method of initial detection in patients with WDTC. This suggests that the prevalence of WDTC detected by imaging is not an artifact caused by an increasingly obese population and that any association of WDTC and obesity is not related to the way in which these tumors are detected.     

大蒜体细胞胚发育分化中特异蛋白和某些生理生化变化（简报）

用改良的MS培养基培养大蒜体细胞胚,获得了稳定且数量较多的成熟胚;用双向电泳分离出5个可能与大蒜胚胎发育有关的特异蛋白质多肽;大蒜酯酶由3个位点的基因控制,其中位点1（Est-1）中的2个复等位基因Est-1e和Est-1f总是连锁表达;位点2种的Est-2b表达产物似可用作大蒜体细胞胚胎发育时期的分子标记;大蒜体细胞胚发生前后,有2个多糖累积高峰,可溶性蛋白的累积仅在球形胚期有1个高峰。     

Variations in Kinematics during Clinical Gait Analysis in Stroke Patients

In addition to changes in spatio-temporal and kinematic parameters, patients with stroke exhibit fear of falling as well as fatigability during gait. These changes could compromise interpretation of data from gait analysis. The aim of this study was to determine if the gait of hemiplegic patients changes significantly over successive gait trials. Forty two stroke patients and twenty healthy subjects performed 9 gait trials during a gait analysis session. The mean and variability of spatio-temporal and kinematic joint parameters were analyzed during 3 groups of consecutive gait trials (1–3, 4–6 and 7–9). Principal component analysis was used to reduce the number of variables from the joint kinematic waveforms and to identify the parts of the gait cycle which changed during the gait analysis session. The results showed that i) spontaneous gait velocity and the other spatio-temporal parameters significantly increased, and ii) gait variability decreased, over the last 6 gait trials compared to the first 3, for hemiplegic patients but not healthy subjects. Principal component analysis revealed changes in the sagittal waveforms of the hip, knee and ankle for hemiplegic patients after the first 3 gait trials. These results suggest that at the beginning of the gait analysis session, stroke patients exhibited phase of adaptation,characterized by a “cautious gait” but no fatigue was observed.