Antitumor activity and transcriptome sequencing (RNA-seq) analyses of hepatocellular carcinoma cells in response to exposure triterpene-nucleoside conjugates.

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 µM), KYSE-150 (IC50 = 5.68 µM), and SW620 (IC50 = 4.61 µM) and along with lower toxicity (TC50 > 100 µM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 µg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 µg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway.

Comparative Chemical Characterization of Potato Powders Using 1H NMR Spectroscopy and Chemometrics.

This study presents the metabolic profiling of potato powders obtained through various processing procedures and commercially available potato powders. The metabolic fingerprinting was conducted using 1H NMR-based metabolomics coupled with machine learning projections. The results indicate hot air-dried potatoes have higher fumarate, glucose, malate, asparagine, choline, gamma aminobutyric acid (GABA), alanine, lactate, threonine, and fatty acids. In comparison, steam-cooked potatoes have higher levels of phenylalanine, sucrose, proline, citrate, glutamate, and valine. Moreover, the contents of metabolites in processed potatoes in this study were higher than those found in commercial potato powders, regardless of the drying or cooking methods used. The results indicate that a new processing technique may be developed to improve the nutritional value of potatoes.

Forecasting HIV-1 Genetic Cluster Growth in Illinois,United States.

BACKGROUND: HIV intervention activities directed toward both those most likely to transmit and their HIV-negative partners have the potential to substantially disrupt HIV transmission. Using HIV sequence data to construct molecular transmission clusters can reveal individuals whose viruses are connected. The utility of various cluster prioritization schemes measuring cluster growth have been demonstrated using surveillance data in New York City and across the United States, by the Centers for Disease Control and Prevention (CDC). METHODS: We examined clustering and cluster growth prioritization schemes using Illinois HIV sequence data that include cases from Chicago, a large urban center with high HIV prevalence, to compare their ability to predict future cluster growth. RESULTS: We found that past cluster growth was a far better predictor of future cluster growth than cluster membership alone but found no substantive difference between the schemes used by CDC and the relative cluster growth scheme previously used in New York City (NYC). Focusing on individuals selected simultaneously by both the CDC and the NYC schemes did not provide additional improvements. CONCLUSION: Growth-based prioritization schemes can easily be automated in HIV surveillance tools and can be used by health departments to identify and respond to clusters where HIV transmission may be actively occurring.

Sorting by Race/Ethnicity Across HIV Genetic Transmission Networks in Three Major Metropolitan Areas in the United States.

An important component underlying the disparity in HIV risk between race/ethnic groups is the preferential transmission between individuals in the same group. We sought to quantify transmission between different race/ethnicity groups and measure racial assortativity in HIV transmission networks in major metropolitan areas in the United States. We reconstructed HIV molecular transmission networks from viral sequences collected as part of HIV surveillance in New York City, Los Angeles County, and Cook County, Illinois. We calculated assortativity (the tendency for individuals to link to others with similar characteristics) across the network for three candidate characteristics: transmission risk, age at diagnosis, and race/ethnicity. We then compared assortativity between race/ethnicity groups. Finally, for each race/ethnicity pair, we performed network permutations to test whether the number of links observed differed from that expected if individuals were sorting at random. Transmission networks in all three jurisdictions were more assortative by race/ethnicity than by transmission risk or age at diagnosis. Despite the different race/ethnicity proportions in each metropolitan area and lower proportions of clustering among African Americans than other race/ethnicities, African Americans were the group most likely to have transmission partners of the same race/ethnicity. This high level of assortativity should be considered in the design of HIV intervention and prevention strategies.

A robust anonymous biometric-based authenticated key agreement scheme for multi-server environments.

In order to improve the security in remote authentication systems, numerous biometric-based authentication schemes using smart cards have been proposed. Recently, Moon et al. presented an authentication scheme to remedy the flaws of Lu et al.'s scheme, and claimed that their improved protocol supports the required security properties. Unfortunately, we found that Moon et al.'s scheme still has weaknesses. In this paper, we show that Moon et al.'s scheme is vulnerable to insider attack, server spoofing attack, user impersonation attack and guessing attack. Furthermore, we propose a robust anonymous multi-server authentication scheme using public key encryption to remove the aforementioned problems. From the subsequent formal and informal security analysis, we demonstrate that our proposed scheme provides strong mutual authentication and satisfies the desirable security requirements. The functional and performance analysis shows that the improved scheme has the best secure functionality and is computational efficient.

Childhood cancer incidence in proximity to nuclear power plants in Illinois.

The objective of this study was to examine childhood cancer incidence in proximity to nuclear power plants in Illinois. Cancer cases diagnosed among Illinois children 0 to 14 years old from 1986 through 2005 were included in the study. Standardized incidence ratio (SIR) was calculated for the geographic zones defined by the proximity to nuclear power plants. The results show that children living within 10 miles of any nuclear power plant did not have significant increase in incidence for leukemia (period 1986-1995: SIR = 0.85 [95% confidence interval, CI: 0.54-1.26]; period 1996-2005: 1.23 [0.91-1.64]), lymphomas [period 1986-1995: 1.38 [0.77-2.27]; period 1996-2005: 0.77 [0.37-1.42]), or other cancer sites. Neither did the children living 10 to 20 miles or 20 to 30 miles from any nuclear power plants. This study did not find any significant childhood cancer excess among children living near nuclear plants and did not observe any dose-response patterns.

Earlier stage at diagnosis and improved survival among Medicare HMO patients with breast cancer.

OBJECTIVE: We sought to evaluate differences in the stage at diagnosis and the survival of breast cancer patients enrolled in two different Medicare healthcare delivery systems: fee for service (FFS) and health maintenance organizations (HMO). METHODS: We used a linkage of two national databases, the Medicare database from the Centers for Medicare and Medicaid Services (CMS), and the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program database, to evaluate differences in demographic data, stage at diagnosis, and survival in patients with breast cancers over the period 1985-2001. RESULTS: Medicare patients enrolled in HMOs were diagnosed at an earlier stage of diagnosis than FFS patients. HMO patients diagnosed with breast cancer had improved survival, and these differences remained even after controlling for potential confounders. Specifically, breast cancer patients enrolled in HMOs had 9% increased probability of survival (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.88-0.93) than their counterparts enrolled in FFS. These findings persisted even when patients had a cancer diagnosis before their breast cancer. CONCLUSIONS: Improved survival among breast cancer patients in HMOs compared with FFS is likely due to a combination of factors, including but not limited to earlier stage at the time of diagnosis.

Changes in the expression of genes associated with intraneuronal amyloid-beta and tau in Alzheimer's disease.

The clinical hallmark of Alzheimer's disease (AD) is impairment of cognition associated with loss of synapses, accumulation of amyloid-beta (Abeta) both within neurons and as extracellular deposits, and neurofibrillary degeneration composed of phospho-tau. Neurons in the hippocampus are among those that are most vulnerable. The purpose of this study was to investigate the expression of genes associated with cognition, synapse, and mitochondrial function in hippocampal neurons of AD compared to normal individuals. Neurons from the hippocampus with intraneuronal Abeta immunoreactivity were captured with laser microdissection; RNA was extracted; and levels of brain-derived neurotrophic factor (BDNF), TrkB (BDNF receptor), dynamin-1 (DYN), and cytochrome C oxidase subunit II (COX2) were assessed with quantitative real-time polymerase chain reaction. We found no significant differences in the expression of these genes in AD between neurons associated with Abeta compared to those lacking Abeta immunoreactivity. Double immunofluorescence microscopy showed the number of hippocampal neurons coexpressing Abeta or phospho-tau and either BDNF, TrkB, or DYN was similar in AD and controls. Our results suggest that neither intraneuronal Abeta nor phospho-tau has obligatory effects on reducing the expression of genes important for memory and cognition in hippocampus of AD.

Disparity in melanoma: a trend analysis of melanoma incidence and stage at diagnosis among whites, Hispanics, and blacks in Florida.

OBJECTIVE: To examine and compare the temporal trends in melanoma incidence and stage at diagnosis among whites, Hispanics, and blacks in Florida from 1990 to 2004. DESIGN: Cross-sectional and retrospective analysis. SETTING: Florida Cancer Data System. PATIENTS: Melanoma cases with known stage and race/ethnicity reported from 1990 to 2004. MAIN OUTCOME MEASURES: Age-adjusted melanoma incidence and stage at diagnosis. RESULTS: Of 41 072 cases of melanoma, 39 670 cases were reported for white non-Hispanics (WNHs), 1148 for white Hispanics (WHs), and 254 for blacks. Melanoma incidence rates increased by 3.0% per year among WNH men (P < .001), 3.6% among WNH women (P < .001), 3.4% among WH women (P = .01), and 0.9% among WH men (P = .52), while remaining relatively stable among black men and women. Both WHs and blacks had significantly more advanced melanoma at presentation: 18% of WH and 26% of black patients had either regional or distant-stage melanoma at diagnosis compared with 12% of WNH patients. The proportion of distant-stage melanoma diagnosed among WHs and blacks changed little from 1990 to 2004, compared with a steady decrease in the percentage of melanoma cases diagnosed at distant stage among WNHs (P < .001). Such differences in the time trends of the proportion of distant-stage melanoma remained after excluding in situ cases. CONCLUSIONS: The rising melanoma incidence among WNHs and WHs emphasizes the need for primary prevention. The persistence of disparity in melanoma stage at diagnosis among WHs, blacks, and WNHs warrants closer examination of secondary prevention efforts in minority groups.

Comparison of the effectiveness of the pulsed dye laser 585 nm versus 595 nm in the treatment of new surgical scars.

UNLABELLED: The aim of this study was to compare the effects of the pulsed-dye laser (PDL) at a wavelength of 585 nm with those at 595 nm in the treatment of post-surgical scars, starting on the day of suture removal. The study was a prospective, non-randomized, double-blind, controlled, clinical trial, set in an outpatient clinic. Fifteen outpatients with 21 post-operative scars at least 3 cm long were recruited, and 14 patients with 19 scars completed the study. Scars were divided into three equal portions. Each outer portion was randomly allocated to PDL at 585 nm or at 595 nm (3.5 J/cm(2), 450 micros, 10 mm spot size), and the center was an untreated control; treatment was composed of three laser sessions at 4-week intervals. A blinded examiner evaluated the three scar sections using the Vancouver scar scale for pigmentation, vascularity, pliability, and height. Cosmetic appearance was evaluated with a visual analog scale. Punch biopsies of three randomly selected scars were evaluated. Pigmentation: more scars after laser treatments were of normal color than in the control, but the difference was not statistically significant. Vascularity: after treatment, more scars had normal vascularity in all three groups than at baseline (P < 0.05); the largest increase was with a wavelength of 585 nm (10.5-94.7%), then 595 nm (15.8-78.9%), then control (5.2-36.6%). Pliability: there was more normal pliability in all three groups than at baseline (P < 0.05), with greater improvements in the laser-treated groups. Height: significantly more flat scars after 585 nm PDL (63.2%) than at baseline (21.1%) (P < 0.05). We observed a slight but non-significant decrease in the scar heights with 595 nm PDL in comparison with the control. HISTOLOGY: after laser irradiation, the treated sections were more similar to a non-scarring process than the control. Cosmetic outcome: visual analog scales increased in all groups (P < 0.05), but the greatest increases were observed in the 585 nm and 595 nm laser-treated groups (50% and 60%, respectively) compared with controls (30%). There were significantly higher scores with the lasers than for the control (P < 0.001) at each visit after baseline. Both the 585 nm and 595 nm PDL treatments were effective in improving the appearance and normalizing the vascularity and pliability of post-operative scars. Both wavelengths improved the scars' visual appearance more than controls. We found that 585 nm appears to be the preferred wavelength, as it substantially normalized the height in addition to the vascularity and pliability in a significant number of scars.

Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality.

OBJECTIVE: To examine the cardiovascular risk factors in patients with psoriasis and the association between psoriasis and coronary artery, cerebrovascular, and peripheral vascular diseases. DESIGN: Observational study. SETTING: Large Department of Veterans Affairs hospital. PATIENTS: The study included 3236 patients with psoriasis and 2500 patients without psoriasis (controls). MAIN OUTCOME MEASURES: Using International Classification of Diseases, Ninth Revision, Clinical Modification, codes, we compared the prevalence of traditional cardiovascular risk factors and other vascular diseases as well as mortality between patients with psoriasis and controls. RESULTS: Similar to previous studies, we found a higher prevalence of diabetes mellitus, hypertension, dyslipidemia, and smoking in patients with psoriasis. After controlling for these variables, we found a higher prevalence not only of ischemic heart disease (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.51-2.11) but also of cerebrovascular (OR, 1.70; 95% CI, 1.33-2.17) and peripheral vascular (OR, 1.98; 95% CI, 1.32-2.82) diseases in patients with psoriasis compared with controls. Psoriasis was also found to be an independent risk factor for mortality (OR, 1.86; 95% CI, 1.56-2.21). CONCLUSIONS: Psoriasis is associated with atherosclerosis. This association applies to coronary artery, cerebrovascular, and peripheral vascular diseases and results in increased mortality.

Tumor necrosis factor-alfa in nonhealing venous leg ulcers.

BACKGROUND: Venous leg ulcers are responsible for more than half of all lower extremity ulcerations, affecting more than one million Americans annually. Studies have demonstrated alterations in levels of proinflammatory cytokines in patients with chronic wounds, including tumor necrosis factor-alfa (TNFalpha), which may be implicated in wound chronicity. OBJECTIVE: To test the hypothesis that recalcitrant venous leg ulcers have increased local tissue TNFalpha as compared to normal skin. METHODS: Five patients with nonhealing healing chronic venous leg ulcers were recruited. Two 4-mm punch biopsy specimens were obtained: one from the wound margin and one from noninvolved, non-sun exposed normal skin on the flexor aspect of the forearm. Tissue samples were processed using fixed with formalin stained by immunohistochemistry for TNFalpha. Qualitative and quantitative comparisons were made for the presence of TNFalpha receptor in all tissue samples, specifically comparing the presence of TNFalpha in nonhealing venous leg ulcer samples versus normal skin. RESULTS: The overall staining score for nonhealing venous leg ulcers was significantly higher compared to respective normal skin samples (P = .01). In addition, immunostaining for TNFalpha was significantly less in the two nonhealing venous leg ulcers that were present for the shortest duration compared to the other ulcers of longer duration (P = .048). LIMITATIONS: The small sample size may mitigate the clinical implications of findings. CONCLUSIONS: Increased levels of TNFalpha in nonhealing venous leg ulcers, especially those of longer duration, implies that excessive inflammation may be causal in wound chronicity and suggests potential therapeutic alternatives.

The ramp power test: a power assessment during a functional task for older individuals.

BACKGROUND: Power is critical to mobility and activities of daily living and is a key determinant of independence and falls prevention. Therefore, the quantification of power in older persons is critical. The power tests currently available are often expensive, potentially dangerous, and not reflective of everyday activities. We present a modification of an existing field test that uses ambulation up a standard access ramp to quantify functional power in older individuals. METHODS: Three hundred sixty-three women and 157 men, aged 73.1 +/- 7.0 years, ambulated up a standard access ramp (1:12 rise/run ratio) as quickly as possible. Each person performed one practice and two timed trials. RESULTS: Comparisons with accepted power measures and reported patterns of change with aging supported the validity of the ramp power test. The test was found to be reliable across multiple trials and days. Pair-wise comparisons showed that for women the test was sensitive to differences in power output by half-decade, whereas for men it could distinguish between 9 of the 15 comparisons among age groups. Percentile scores are reported by half-decade for power in both genders. In > 1200 trials performed during this study, only one injury (a slightly strained hamstring) occurred. CONCLUSIONS: The ramp power test is valid and reliable and can safely distinguish power by half-decade in women and among the majority of age groups in men. Its safety, low cost, and ease of administration make it a feasible diagnostic tool to assess functional power levels in ambulatory older persons.

Predictors of skin cancer screening practice and attitudes in primary care.

BACKGROUND: Physician visits provide invaluable opportunities to screen patients for skin cancer, yielding earlier detection and improved survival. OBJECTIVE: We sought to assess frequency of skin cancer screening by full body skin examinations (FBSE) by primary care physicians, patient attitudes toward FBSE, and risk factors for cutaneous malignancy. METHODS: Questionnaires were distributed to patients at primary care and dermatology clinics. RESULTS: A total of 426 participants were surveyed. Overall, 20% of patients reported having undergone regular FBSE by their primary care physician. Sex, race, personal skin cancer history, and Fitzpatrick skin type were predictive of whether a FBSE was performed by a patient's primary care physician. Men were more likely to report having undergone a FBSE (22% vs 19%; P < .01); women were more likely to report feeling embarrassed by a FBSE (15% vs 4%; P < .01). LIMITATIONS: This study was conducted at a single site academic center. CONCLUSION: Although low rates of skin cancer screening are reported by patients, those at higher risk are being screened more frequently. Sex disparity exists, and as both male and female patients have a strong preference to undergo FBSE, unmet opportunities for skin cancer prevention should be maximized.

Care coordination and telemedicine improves glycaemic control in ethnically diverse veterans with diabetes.

We conducted a pilot study of a care-coordination programme involving daily monitoring and education of elderly diabetic veterans from different racial/ethnic groups. A telephone-based, in-home messaging device was used for patient monitoring and education. Sixty-nine patients were enrolled in the study and HbA(1c) values were obtained both before and after the telemedicine intervention in 41 of them. The mean HbA(1c) before enrolment was 7.6% and the mean value 9 months later was 7.3% (P = 0.09). The greatest fall in HbA(1c) occurred in African-Americans (0.65%, P = 0.05). The total number of hospital admissions decreased from 31 pre-enrolment to 25 post-enrolment (P = 0.0002). Bed days of care decreased from 368 to 149 (P = 0.0002). Care coordination, facilitated by telemedicine, appeared to improve glycaemic control in veterans with diabetes from diverse ethnic backgrounds, particularly African-Americans. This may reduce health-care resource utilization.

Scapular stabilizer activity during Bodyblade, cuff weights, and Thera-Band use.

CONTEXT: There are numerous ways to overload the scapular stabilizers. OBJECTIVES: To assess scapular stabilizer activity using the Bodyblade and other traditional training devices. DESIGN: Repeated measures analysis of surface EMG data collected from the upper trapezius (UT), lower trapezius (LT), and serratus anterior (SA) during shoulder flexion and abduction using Bodyblade, cuff weight, and Thera-Band resistance. SETTING: Laboratory. PARTICIPANTS: Thirty collegiate athletes (20.0 +/- 1.7 years). INTERVENTION: Participants performed 10 repetitions of shoulder flexion and abduction. MAIN OUTCOME MEASURES: For each movement, normalized root mean square values (NrmsEMG) were computed for each muscle during each repetition under each training condition. Data were analyzed using 3 (condition) 3 10 (repetition) repeated measures ANOVAs. RESULTS: During shoulder flexion and abduction, the NrmsEMG of the UT, LT, and SA were significantly greater when using the Bodyblade than the Thera-Band or cuff weight. CONCLUSION: The Bodyblade produces greater scapular activity than traditional resistance techniques.

Skin cancer awareness and sun protection behaviors in white Hispanic and white non-Hispanic high school students in Miami, Florida.

OBJECTIVE: To examine skin cancer awareness and behavior in white Hispanic (WH) and white non-Hispanic (WNH) high school students because increasing incidence and delayed diagnosis of skin cancer in the growing Hispanic population in the United States represent an emerging health issue. DESIGN: Pilot survey study. SETTING: A high school in Miami, Florida. PARTICIPANTS: A total of 369 high school students (221 WHs and 148 WNHs) were surveyed in the study. MAIN OUTCOME MEASURES: Survey data were collected regarding skin cancer knowledge, perceived risk, and sun protection behaviors. Differences between the 2 groups were compared with chi(2) tests. RESULTS: White Hispanic students were more likely to tan deeply (P = .04) but less likely to have heard of (P < .01) or been told how to perform (P < .01) skin self-examination. White Hispanics were less likely to wear sun-protective clothing or to use sunscreen with a sun protection factor of 15 or higher and reported a greater use of tanning beds. White Hispanic students also thought their chance of developing skin cancer was less than that of WNH students (P < .01), which remained significant after adjustment for age, sex, family history, and skin sensitivity to sun. After adjustment, WHs were 2.5 times more likely than WNHs to have used a tanning bed in the past year. White Hispanics were also 60% less likely to have heard of skin self-examination (P < .01) and 70% less likely than WNHs to have ever been told to perform the examination (P = .03). White Hispanics are about 1.8 and 2 times more likely to never or rarely wear protective clothing (P < .01) and to use sunscreen (P = .01), respectively. CONCLUSION: There are disparities in knowledge, perceived risk of skin cancer, and sun-protective behaviors among WH and WNH high school students.

The gallon-jug shelf-transfer test: an instrument to evaluate deteriorating function in older adults.

This study examined the validity, reliability, and discriminatory capacity of the gallon-jug shelf-transfer (GJST) test. Six hundred fifty-three independent-living older adults (463 women age 72.9 +/- 7.0 years, 190 men age 74.3 +/- 6.7 years) participated. Participants moved five 1-gallon jugs (approximately 3.9 kg) from a knee-high to a shoulder-high shelf as quickly as possible. The GJST showed an exponential performance decline with age, and there were significant correlations between the GJST and common functional tests (p<.001). High within-day and between-days reliability was detected. The test also detected differences resulting from training status (p<.01) and training protocols (p<.05). The GJST is a valid, reliable, inexpensive, safe, and easily administered clinical test for identifying physically vulnerable elders who could benefit from interventions such as exercise to improve their physical capacities and maintain independence.