Nanoscale field effect transistor for biomolecular signal amplification

We report amplification of biomolecular recognition signal in lithographically defined silicon nanochannel devices. The devices are configured as field effect transistors (FET) in the reversed source-drain bias region. The measurement of the differential conductance of the nanowire channels in the FET allows sensitive detection of changes in the surface potential due to biomolecular binding. Narrower silicon channels demonstrate higher sensitivity to binding due to increased surface-to-volume ratio. The operation of the device in the negative source-drain region demonstrates signal amplification. The equivalence between protein binding and change in the surface potential is described

Field Effect Transistor Nanosensor for Breast Cancer Diagnostics

Silicon nanochannel field effect transistor (FET) biosensors are one of the most promising technologies in the development of highly sensitive and label-free analyte detection for cancer diagnostics. With their exceptional electrical properties and small dimensions, silicon nanochannels are ideally suited for extraordinarily high sensitivity. In fact, the high surface-to-volume ratios of these systems make single molecule detection possible. Further, FET biosensors offer the benefits of high speed, low cost, and high yield manufacturing, without sacrificing the sensitivity typical for traditional optical methods in diagnostics. Top down manufacturing methods leverage advantages in Complementary Metal Oxide Semiconductor (CMOS) technologies, making richly multiplexed sensor arrays a reality. Here, we discuss the fabrication and use of silicon nanochannel FET devices as biosensors for breast cancer diagnosis and monitoring

Health-Related and Sociodemographic Correlates of Meeting the Muscle Strengthening Exercise Recommendations in Middle-Aged and Older Adults with and without Disabilities

ut disabilities Shirit Kamil-Rosenberg, Mary L. Greaney & Carol Ewing Garber Sport Sciences for Health (2020)Cite this article 51 Accesses 4 Altmetric Metricsdetails Abstract Purpose To identify sociodemographic and health correlates of meeting the muscle strengthening (MS) exercise recommendations in middle-aged and older adults by disability status. Methods Respondents from the 2011 Behavioral Risk Factor Surveillance System were stratified by disability status (with disability, without disability), age [ages 45–64 (middle-aged), 65 + years of age (older adults)] and whether they met MS recommendations (yes, no). Two logistic regression models were run to evaluate whether perceived health status and sociodemographic characteristics were associated with meeting the MS recommendations by disability status. Results The sample included 477,662. Middle-aged persons were 20% more likely than older adults to meet the MS recommendations. Persons with a disability were less likely to meet muscle strengthening recommendations compared with those without. Persons with a disability who reported having poor health were ~ 65% less likely to meet the MS recommendation than those reporting excellent health. Furthermore, those with a disability and with one or more chronic diseases were nearly 40% less likely to meet the MS recommendation than no disability. Among respondents without disability, being Black and being a healthy weight or underweight increased the odds of meeting the MS recommendations. Conclusion Several health and sociodemographic factors were associated with not meeting MS recommendations. Persons with disability and poor health, had the lowest likelihood of participation. Studies are needed to understand whether improving MS exercise behavior may attenuate functional limitations associated with chronic diseases and aging

CDKN1C/p57kip2 Is a Candidate Tumor Suppressor Gene in Human Breast Cancer

BACKGROUND. CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. METHODS. We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. RESULTS. AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2–60% of paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20 (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and 5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss of CDKN1C expression from myoepithelial layer cells, which stained intensely in 17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast, luminal cells displayed less intense, focal staining fairly consistently across histologies. Decreased CDKN1C was not clearly associated with tumor grade, histology, ER, PR or HER2 status. CONCLUSION. CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor.Department of Defense Breast Cancer Research Program (DAMD 17-99-1-9573); National Institutes of Health PHS (CA081078); LaPann Fun

PRAD1 (Cyclin D1): A Parathyroid Neoplasia Gene on 11q13

Hyperparathyroidism is a central component of multiple endocrine neoplasia type 1 (MEN 1), and both sporadic and familial forms of parathyroid disease may share certain pathogenetic features. We recently identified a gene that is clonally rearranged with the PTH locus in a subset of sporadic parathyroid adenomas. This candidate oncogene, PRAD1 (previously D11S287), appears to contribute to parathyroid tumorigenesis in a fashion analogous to activation of C-MYC or BCL-2 by rearrangement with tissue-specific enhancers of the immunoglobulin genes in B-lymphoid neoplasia. The PRAD1 gene maps to 11q13 and has been linked to the BCL-1 breakpoint locus, although not to the most tightly linked MEN 1 markers, by pulsed field gel electrophoresis. PRAD1 may, in fact, be the long-sought BCL-1 lymphoma oncogene. PRAD1 encodes a novel type of cyclin protein and thus may normally function in controlling the cell cycle, perhaps through direct interaction with cdc2 or a related kinase. PRAD1\u27s possible primary, or more likely secondary, involvement in the pathogenesis of MEN 1-related tumors is unknown and under investigation

A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study

BACKGROUND: Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified. METHODS: We conducted a genome-wide association study (Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits – prostate cancer and breast cancer – in up to 1335 participants from 330 families (54% women, mean entry age 33 years). Multivariable-adjusted residuals, computed using Cox proportional hazards models, were tested for association with qualifying SNPs (70, 987 autosomal SNPs with genotypic call rate ≥80%, minor allele frequency ≥10%, Hardy-Weinberg test p ≥ 0.001) using generalized estimating equations (GEE) models and family based association tests (FBAT). RESULTS: There were 58 women with breast cancer and 59 men with prostate cancer. No SNP associations attained genome-wide significance. The top SNP associations in GEE models for each trait were as follows: breast cancer, rs2075555, p = 8.0 × 10-8 in COL1A1; and prostate cancer, rs9311171, p = 1.75 × 10-6 in CTDSPL. In analysis of selected candidate cancer susceptibility genes, two MSR1 SNPs (rs9325782, GEE p = 0.008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs (rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0.0078) were associated with breast cancer. The previously reported risk SNP for prostate cancer, rs1447295, was not included on the 100K chip. Results of cancer phenotype-genotype associations for all autosomal SNPs are web posted at. CONCLUSION: Although no association attained genome-wide significance, several interesting associations emerged for breast and prostate cancer. These findings can serve as a resource for replication in other populations to identify novel biologic pathways contributing to cancer susceptibility.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1

Risk factors for common cancers among patients at Kamuzu Central Hospital in Lilongwe, Malawi: A retrospective cohort study

Little is known about risk factors for different cancers in Malawi. This study aimed to assess risk factors for and epidemiologic patterns of common cancers among patients treated at Kamuzu Central Hospital (KCH) in Lilongwe, and to determine the prevalence of Human Immunodeficiency Virus (HIV) infection in the same population

Sexual exploitation in children: Nature, prevalence and distinguishing characteristics reported in young adulthood

The aim of this study was to explore the nature and extent of sexual exploitation in a university student sample, whilst being clear that sexual exploitation is sexual abuse. Overall, 47% of participants (96 out of 204) reported having been approached by an adult in a sexual manner when they were under the age of 16. The study predicted that a number of individual characteristics would increase a young person’s vulnerability for sexual exploitation. These included low self-esteem, external locus of control, social loneliness and insecure attachment. Results indicated lower levels of self-esteem among those who had been approached sexually, although it is not clear in terms of causality. There were no differences in scores for locus of control or loneliness. Relationship anxiety was significantly linked with children having engaged in sexual behaviours with an adult. The implications of these findings are discussed in terms of emerging individual characteristics relating to a risk of sexual exploitation

Risk factors for common cancers among patients at Kamuzu Central Hospital in Lilongwe, Malawi: A retrospective cohort study

Background: Little is known about risk factors for different cancers in Malawi. This study aimed to assess risk factors for and epidemiologic patterns of common cancers among patients treated at Kamuzu Central Hospital (KCH) in Lilongwe, and to determine the prevalence of Human Immunodeficiency Virus (HIV) infection in the same population.Methods: We analysed data from the hospital-based KCH cancer registry, from June 2009 to September 2012, including data from a nested substudy on coinfections among cancer patients. Demographics and behavioural variables, including smoking and alcohol use, were collected through personal interviews with patients. We assessed HIV prevalence across cancer types. The distribution of cancer types was reported overall and by gender. Logistic regression was used to assess risk factors associated with common cancer types.Results: Data from 504 registered cancer patients were included—300 (59.5%) were female and 204 (40.5%) were male. Mean age was 49 years (standard deviation, SD = 16). There were 343 HIV-negative patients (71.2%), and 139 (28.8%) were HIV-positive. The commonest cancers were oesophageal (n = 172; 34.5%), cervical (n = 109; 21.9%), and Kaposi’s sarcoma (KS) (n = 52; 10.4%). Only 18% of cancer cases were histologically confirmed. Patients with oesophageal cancer were likely to be older than 50 years (odds ratio, OR = 2.22), male (OR = 1.47), and smokers (OR = 2.02). Kaposi’s sarcoma patients had the highest odds (OR = 54.4) of being HIV-positive and were also more likely to be male (OR = 6.02) and smokers. Cervical cancer patients were more likely to be HIV-positive (OR = 2.2) and less than 50 years of age.Conclusions: Age, smoking, and HIV are important risk factors for the 3 commonest cancer types (oesophageal, KS, and cervical) at this teaching hospital in Malawi. HIV is the single most important risk factor for Kaposi’s sarcoma and cervical cancer