Sub-cellular force microscopy in single normal and cancer cells.

This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures.

The fractional viscoelastic response of human breast tissue cells.

The mechanical response of a living cell is notoriously complicated. The complex, heterogeneous characteristics of cellular structure introduce difficulties that simple linear models of viscoelasticity cannot overcome, particularly at deep indentation depths. Herein, a nano-scale stress-relaxation analysis performed with an atomic force microscope reveals that isolated human breast cells do not exhibit simple exponential relaxation capable of being modeled by the standard linear solid (SLS) model. Therefore, this work proposes the application of the fractional Zener (FZ) model of viscoelasticity to extract mechanical parameters from the entire relaxation response, improving upon existing physical techniques to probe isolated cells. The FZ model introduces a new parameter that describes the fractional time-derivative dependence of the response. The results show an exceptional increase in conformance to the experimental data compared to that predicted by the SLS model, and the order of the fractional derivative (α) is remarkably homogeneous across the populations, with a median value of 0.48 ± 0.06 for the malignant population and 0.51 ± 0.07 for the benign. The cells' responses exhibit power-law behavior and complexity not associated with simple relaxation (SLS, α = 1) that supports the application of a fractional model. The distributions of some of the FZ parameters also preserve the distinction between the malignant and benign sample populations seen from the linear model and previous results while including the contribution of fast-relaxation behavior. The resulting viscosity, measured by a composite relaxation time, exhibits considerably less dispersion due to residual error than the distribution generated by the linear model and therefore serves as a more powerful marker for cell differentiation.

IgA nephropathy in the triethnic population of New Mexico.

AIMS: IgA nephropathy (IgAN) is the most frequent glomerulonephritis around the globe, but its incidence in the United States is unknown. The disease has a preponderance for certain racial/ethnic groups. Our goals were to retrospectively analyze a series of IgAN biopsies from the state of New Mexico and to calculate an estimated incidence. Then we compared the racial/ethnic composition of our patient cohort to the composition of the New Mexico population and examined the three main racial/ethnic groups for differences in clinical and pathologic parameters. MATERIALS AND METHODS: Renal biopsies and clinical data from IgAN cases newly diagnosed in New Mexico between 2000 and 2005 were reviewed. We compared the racial/ethnic composition of our patient cohort to the demographic composition of the New Mexico population. Demographic, clinical, and histopathologic variables were analyzed with respect to the patients' race/ethnicity. RESULTS: The incidence of IgAN in New Mexico was 10.2 cases per million persons per year (9.3 when Henoch-Schönlein purpura cases were excluded). American Indians were twice as frequent in our patient cohort when compared to their demographic representation, with the reverse finding for Non-Hispanic Whites. Hispanics more frequently had nephrotic range proteinuria than Non-Hispanic Whites and American Indians. On renal biopsy, endocapillary proliferative glomerulonephritis was the most common glomerular abnormality, followed by the focal segmental glomerulosclerosis (FSGS)-like pattern. The FSGS-like pattern was more frequent in American Indians and Hispanics than in Non-Hispanic Whites. CONCLUSIONS: This is the first report of an incidence figure of IgAN for an entire state in the US. American Indian and Hispanic patients had a stronger representation in our cohort than Non-Hispanic Whites, when compared to the general New Mexico population.

The Human Genome Project--threat or promise?

This paper reflects on some of the arguments against screening from the perspective of a relative of individuals with Fragile X syndrome. It proposes to think about intellectual disability (ID) as including a wide range of limitations beyond that of only the mental handicap. It argues that these limitations impose conditions upon both people with disabilities and their parents, as well as upon their siblings, that in various ways amount to suffering. The claim that people with disabilities are enriching the lives of their relatives is rejected. Furthermore, it is argued that those who ascribe a high moral status to people with disabilities tend to neglect that society does not make much of an effort to offer the necessary support to materialize this status. The claim that screening negatively affects the moral status of persons with ID is rebutted on grounds of the freedom of choice.

An assessment of screening strategies for fragile X syndrome in the UK.

BACKGROUND: Fragile X syndrome is an inherited form of learning disability that was defined in the late 1970s by cytogenetic detection of an associated fragile site on the X chromosome (Xq27.3). Cytogenetic estimates of the prevalence of fragile X syndrome were as high as 1 in 1039 males but have since been revised downwards. Fragile X syndrome is associated with few medical problems and the subtle physical features make clinical diagnosis difficult. The unusual pattern of inheritance, delineated in the 1980s, was explained once the fragile X syndrome gene (FMR1) had been identified in 1991. This gene contains a highly variable repeat of the nucleotide triplet, cytosine-guanine-guanine (CGG). Fragile X syndrome is caused by a large expansion of this CGG repeat (full mutation) that leads to silencing of the FMR1 gene so no gene product (FMRP) is made. This is the ultimate cause of the learning disability that, in males, is sufficient to preclude independent living. Family studies show that all individuals with a full mutation inherit it from a female (usually unaffected) who carries either a full mutation or a premutation, a smaller repeat expansion (approximately 55-200 repeats) that is unstable on female transmission. The chance of a premutation expanding to a full mutation is positively associated with the size of the repeat (approximately 95% by 90 repeats) but only for female transmissions. When a man transmits a premutation, it remains a premutation; his children are, therefore, unaffected by overt learning difficulties. The potential for population screening or systematic case-finding and extended family testing exists because every unaffected mother of an affected child has a detectable CGG repeat expansion. Reliable prenatal diagnosis is possible in males. OBJECTIVES: To assess the feasibility and acceptability of population screening by addressing the following questions in the context of existing services for families with fragile X syndrome. (1) Is there a suitable test for all fragile X genotypes? (2) What are the UK population distribution of FMR1 repeat sizes, and the prevalence of full and premutations in both sexes? (3) What reliable information, in terms of the chance of an affected child, is available to women with premutations between 55 and 200 repeats? (4) What is the effect of a premutation on the person who carries it? (5) What information is available to women with intermediate alleles of 41 to 54-60 repeats? (6) How many affected people are diagnosed? (7) Given the practice of offering extended family testing (cascade testing), what is the population prevalence of 'as-yet-undiagnosed' female carriers of a full or premutation? What proportion of women at risk can be reached by cascade testing? (8) What are the costs of fragile X syndrome to an affected person and their family and to the NHS and society? (9) What is the attitude of families to the benefits and costs of a diagnosis of fragile X syndrome, and to the prospect of population screening? (10) What data are available from existing population screening programmes? (11) What alternatives to population screening exist and are these feasible? METHODS: A key aspect of the review process was to assemble a team with extensive first-hand experience of all aspects of fragile X syndrome, including affected families and the services they use, and a wide knowledge of the relevant literature. They had followed the critical discussions at all the biennial international workshops on fragile X syndrome, including a special session at the 7th International Workshop in 1995 at which an earlier (and substantially different) draft of this report was discussed. The biomedical literature review of 2429 papers was based on MEDLINE searches, extending to PsycINFO and BIDS for the psychological aspects of [fragile X syndrome] screening. Questionnaire-based information was obtained from the UK Fragile X Society and data were collected directly from all the regional clinical genetics centres in 1995 and 1998. RESULTS: Unlike cytogenetic approaches, DNA analysis can reliably determine the FMR1 CGG repeat number and detect full mutations; however, a combination of polymerase chain reaction and Southern blotting tests is required, which limits high throughput. There are UK population-based data on FMR1 repeat sizes of up to 60 repeats but insufficient to provide a reliable estimate of the prevalence of premutations (approximately 60-200 repeats). The few data and estimates in the literature of women carriers of the premutation range from 1 in 246 to 1 in 550. Two UK DNA-based estimates of the prevalence of males with the full mutation are 1 in 4090 (Coventry) and 1 in 5530 (Wessex). There are reasonable family-based data for the risk of expansion to a full mutation for the larger premutations but in the 50-69 repeat range the estimates are less secure. (ABSTRACT TRUNCATED)

Primary tumors of the spine.

Primary osseous tumors of the spine are rare lesions and much less frequently encountered than metastases, multiple myeloma, and lymphoma. The interpreting radiologist must be aware of the typical radiographic appearance of the most common nonmyeloproliferative tumors of the spine because these tumors must be considered when a solitary spinal lesion is encountered. The purpose of this article is to describe the radiologic appearance and radiologic staging of the most common benign (hemangioma, enostosis, osteoid osteoma, osteoblastoma, giant cell tumor, aneurysmal bone cyst, and osteochondroma) and malignant (chordoma, chondrosarcoma, Ewing tumor, and osteosarcoma) osseous spine tumors.

Diagnosis of fragile-X syndrome: the experiences of parents.

In order to assess some aspects of the quality of care for families seeking the cause of their child(ren)s intellectual disability, a postal questionnaire was sent to parents of children with fragile-X syndrome, who were members of the UK Fragile-X Society. Although the interval taken to get a diagnosis ('lagtime') has fallen over time, other aspects of care could still be improved. Most families feel that having a diagnosis is an advantage, but many still find the diagnostic process distressing and feel unsupported. Not all families are referred for genetic counselling, and even those who are do not always understand or retain the information given. Most families feel that having a diagnosis is a benefit rather than a disadvantage.

High-resolution brain SPECT imaging in ADHD.

Children and adolescents with ADHD were evaluated with high-resolution brain SPECT imaging to determine if there were similarities between reported PET and QEEG findings. Fifty-four children and adolescents with ADHD by DSM-III-R and Conners Rating Scale criteria were evaluated. A non-ADHD control group was also studied with SPECT. Two brain SPECT studies were done on each group, a resting study and an intellectual stress study done while participants were doing a concentration task. Sixty-fiver percent of the ADHD group revealed decreased perfusion in the prefrontal cortex with intellectual stress, compared to only 5% of the control group. These are findings consistent with PET and QEEG findings. Of the ADHD group who did not show decreased perfusion, two-thirds had markedly decreased activity in the prefrontal cortices at rest.

Business process reengineering: a remedy for health care.

Health care organizations are facing significant economic constraints that threaten to dismantle core services. The perceived need for reform is great. Business process reengineering may be the strong medicine required to achieve dramatic productivity improvement without jeopardizing the quality and scope of core health care services. Reengineering challenges health care organizations to eliminate functions that do not contribute to a flattened organization structure in which fewer care providers deliver a wider range of health care services. Information technology is used to displace manual checks and controls. Reengineering may facilitate the implementation of contemporary management models, such as patient-focused care, case management and product or program management. The product of reengineering can be enhanced over time by Continuous Quality Improvement.

Implications of new accounting rules for income taxes.

The provisions of the Financial Accounting Standards Board (FASB) Statement No. 109, Accounting for Income Taxes, require all organizations that issue financial statements to shift the focus of their accounting for income taxes from the income statement to the balance sheet. This change can alter significantly a healthcare organization's financial position. The change also may affect the way in which investors, lenders, regulators, and other users of financial statements evaluate corporations in the healthcare industry. Hospitals and other healthcare organizations, particularly for-profit organizations, therefore, should review carefully their methods of accounting for such items as deferred tax assets and loss and expense reserves.

Influence of birth weight on adult bone mineral density.

Bone mineral density (BMD) increases during growth until a peak is reached at maturity. The risk of development of postmenopausal osteoporosis depends on the peak bone density and the rate of its subsequent loss. To identify whether low weight at birth could affect the peak bone density, we measured BMD at both the lumbar spine and femoral neck using dual energy X-ray absorptiometry (DXA) in a group of women who had low weight at birth and in a control group of normal birth weight. There was no significant correlation between the weight at birth and the adult BMD. It appears, therefore, that low weight at birth does not influence the peak bone density and that prematurity is not a risk factor for osteoporosis.