Low Rates of Colorectal Cancer Screening in First-Degree Relatives of Our Patients: Are We Failing Them?

BACKGROUND: Guidelines recommend screening those with a family history of early-onset colorectal cancer at age 40 years or 10 years before the age of their relative's diagnosis. Currently, there is no literature reporting the screening rate in these individuals, and no protocols are in place to identify and target this population for screening awareness. OBJECTIVE: This study aimed to assess adherence to current screening guidelines among first-degree relatives of patients with early-onset colorectal cancer. DESIGN: Retrospective and qualitative study involving a telephone survey where patients were asked about relative's screening status and barriers to screening. SETTINGS: Two community-based institutions between January 2018 and December 2021. PATIENTS: Individuals diagnosed with early-onset colorectal cancer who had undergone surgery at our institutions. MAIN OUTCOME MEASURES: Rate of screening in first-degree relatives of our patients with early-onset colorectal cancer. Other factors measured included demographics, clinicopathologic characteristics, and screening barriers. RESULTS: Thirty-six patients were identified. The survey response rate was 66.6% (n = 24). A total of 88 first-degree relatives who met the screening criteria resulted in 67.1% of patients (n = 59) having a known screening status. Of the 59 patients with known screening status, only 44% (n = 26) had undergone screening. Patients of Black race, having stage III/IV disease, having Medicare/Medicaid insurance, and living within Baltimore City County were more likely to have family members with unknown or no screening. Lack of insurance coverage was the most common barrier, which was noted in 12.5% of patients (n = 3), whereas 54.1% of patients (n = 13) reported no barriers to screening. LIMITATIONS: Retrospective design. CONCLUSIONS: Most first-degree relatives of patients diagnosed with early-onset colorectal cancer do not undergo colorectal cancer screening. This could be attributed to the lack of protocols that could guarantee these individuals are informed of their elevated risk and the different options available for screening. Furthermore, our study suggests that racial and socioeconomic disparities exist among high-risk patients who should pursue screening. See Video Abstract . BAJAS TASAS DE DETECCIN DEL CNCER COLORRECTAL EN LOS FAMILIARES DE PRIMER GRADO DE NUESTROS PACIENTES LES ESTAMOS FALLANDO: ANTECEDENTES:Las directrices recomiendan realizar pruebas de detección a las personas con antecedentes familiares de cáncer colorrectal de aparición temprana a los 40 años o 10 años antes de la edad del diagnóstico de su familiar. Actualmente, no hay literatura que informe la tasa de detección en estos individuos y no existen protocolos para identificar y dirigirse a esta población para concientizar sobre la detección.OBJETIVO:Evaluar el cumplimiento de las pautas de detección actuales entre los FDR de pacientes con cáncer colorrectal de aparición temprana.DISEÑO:Estudio retrospectivo y cualitativo que incluyó una encuesta telefónica en la que se preguntó a los pacientes sobre el estado de detección de sus familiares y las barreras para la detección.AJUSTES:Dos instituciones comunitarias entre enero de 2018 y diciembre de 2021.PACIENTES:Personas diagnosticadas con cáncer colorrectal de inicio temprano que habían sido intervenidas quirúrgicamente en nuestras instituciones.PRINCIPALES MEDIDAS DE RESULTADO:Tasa de detección en familiares de primer grado de nuestros pacientes con cáncer colorrectal de aparición temprana. Otros factores medidos incluyeron datos demográficos, características clínico-patológicas y barreras de detección.RESULTADOS:Se identificaron treinta y seis pacientes. La tasa de respuesta a la encuesta fue del 66,6% (n = 24). Resultaron un total de 88 familiares de primer grado que cumplieron con los criterios para la detección, y el 67,1% (n = 59) tenía un estado de detección conocido. De los 59 con estado de detección conocido, se informó que solo el 44% (n = 26) se había sometido a pruebas de detección. Los pacientes de raza afroamericana, enfermedad en etapa III/IV, Medicare/Medicaid y que vivían dentro del condado de la ciudad de Baltimore tenían más probabilidades de tener familiares con pruebas de detección desconocidas o sin ellas. La falta de cobertura de seguro fue la barrera más común observada por el 12,5% (n = 3); mientras que el 54,1% (n = 13) no informó ninguna barrera para el cribado.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:La mayoría de los familiares de primer grado de pacientes diagnosticados con cáncer colorrectal de aparición temprana no se someten a pruebas de detección de cáncer colorrectal. Esto podría atribuirse a la falta de protocolos que garanticen que estas personas estén informadas sobre su elevado riesgo y las diferentes opciones disponibles para el cribado. Además, nuestro estudio sugiere que existen disparidades raciales y socioeconómicas entre los pacientes de alto riesgo que deberían someterse a pruebas de detección. (Traducción-Dr. Francisco M. Abarca-Rendon).

An Update on Fetal Alcohol Syndrome-Pathogenesis, Risks, and Treatment.

Alcohol is a well-established teratogen that can cause variable physical and behavioral effects on the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome (FAS). The differences in maternal and fetal enzymes, in terms of abundance and efficiency, in addition to reduced elimination, allow for alcohol to have a prolonged effect on the fetus. This can act as a teratogen through numerous methods including reactive oxygen species (generated as by products of CYP2E1), decreased endogenous antioxidant levels, mitochondrial damage, lipid peroxidation, disrupted neuronal cell-cell adhesion, placental vasoconstriction, and inhibition of cofactors required for fetal growth and development. More recently, alcohol has also been shown to have epigenetic effects. Increased fetal exposure to alcohol and sustained alcohol intake during any trimester of pregnancy is associated with an increased risk of FAS. Other risk factors include genetic influences, maternal characteristics, for example, lower socioeconomic statuses and smoking, and paternal chronic alcohol use. The treatment options for FAS have recently started to be explored although none are currently approved clinically. These include prenatal antioxidant administration food supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors. Tackling the wider impacts of FAS, such as comorbidities, and the family system have been shown to improve the quality of life of FAS patients. This review aimed to focus on the pathogenesis, especially mechanisms of alcohol teratogenicity, and risks of developing FAS. Recent developments in potential management strategies, including prenatal interventions, are discussed.

Reducing tobacco use among low socio-economic status youth in Delhi, India: outcomes from project ACTIVITY, a cluster randomized trial.

To test the efficacy of an intervention to reduce tobacco use among youth (10-19 years old) in slum communities in Delhi, India. This community-based cluster-randomized trial included 14 slums composed of purposely built resettlement colonies and adjacent inhabitant-built Jhuggi Jhopris. Youth in the intervention received a 2 year multiple-component intervention: (a) youth and adult leader training; (b) peer-led interactive activities and outreach; (c) tobacco cessation camps; and (d) enforcement of India's Tobacco Control Law (smoke-free environments and youth access). Overall, no differences between the intervention and control conditions were observed over time; self-reported tobacco use declined in both groups. However, when stratified by type of residence, a significant decrease was observed among youth in the resettlement colonies in the intervention group for overall tobacco use (slope = -0.69) and cigarette and bidi smoking (slope = -0.66), compared to an increase in the control group (slope = 0.24 and 0.12, respectively) (P < 0.001). No differences in smokeless tobacco (SLT) use were observed for either group. Comprehensive community-based interventions that engage youth can be effective in reducing smoking among disadvantaged youth in India. More intensive interventions, like tax increases or large-scale media campaigns, appear warranted for the most marginalized in this context and for SLT products.

Fluorometric assay to compensate for non-viable cells during electroporation.

A fluorometric assay is described that allows adjustment for non-viable cells that result during electroporation. The technique, unlike others, relies on only one dye, requires a single instrument, and eliminates the need for a separate cell counting step. Murine melanoma (B16-F10) cells were electroporated using electric fields ranging from 400 to 2500 V/cm in the presence of SYTOX(®)-green. Compensation for the fluorescence resulting from non-viable cells was facilitated by a correction curve established by lysing a known number of cells in the presence of SYTOX(®)-green. In uncorrected data, an applied electric field of 2500 V/cm increased dye delivery but also reduced cell viability significantly. Compensating for the fluorescence of non-viable cells showed that changing the field strength to 800 V/cm or 2500 V/cm from 400 V/cm had only marginal effects on membrane pore formation. The fluorometric assay was used to compare electroporation in high conductivity (PBS) and a low conductivity medium (LC-PBS). Statistically significant increases of 10 to 30-fold were observed for cells electroporated at 400 V/cm and 800 V/cm in LC-PBS.

Control and support models of help-seeking behavior in women experiencing domestic violence in India.

In India, there is limited prioritization of domestic violence, which is seen as a private and family matter, and handled as a social responsibility rather than a complaint or crime. Despite the Domestic Violence Act, implemented in 2006, the widespread phenomenon of domestic violence across Indian states goes unreported. Using control and support models, this article aims to examine women's behavior in seeking help while dealing with partner violence. It is a population-based analytical cross-sectional study covering 14,507 married women from 18 states of India, selected through a systematic multistage sampling strategy. Both quantitative and qualitative methods were used to generate data. It was observed that legal complexities combined with social realities make the life of an average Indian woman insecure and miserable. Most women surveyed preferred the social-support model and opined that if they face domestic violence, they would seek help from their parents as the first option in the order of preference. The responses of women while dealing with domestic violence are often spontaneous and determined by the pressing need to resolve matters within the home/community, rather than addressing them in the public domain of state institutions where procedures are cumbersome and lengthy. A new integrated development model proposed by several communities aims to prevent domestic violence through the intervention of health care systems.

Impact of Surgical Resident Education and EMR Standardization in Enhancing ERAS Adherence and Outcomes in Colorectal Surgery.

OBJECTIVE: Our study aimed at investigating the degree of adherence to ERAS pathway at our institution and to evaluate the role of providing resident education and a standardized EMR order set in improving adherence and patient surgical outcomes. DESIGN: The study is prospective in nature and consists of two phases with a preintervention cohort to assess adherence to ERAS protocol and a postintervention cohort to evaluate improvement in adherence and patient outcomes. Adherence with the ERAS protocol was assessed across preoperative, intraoperative, and postoperative phases. SETTING: The study took place at MedStar Franklin Square Medical Center in Baltimore, Maryland, involving inpatient care at a surgical ward. PARTICIPANTS: During the preintervention phase, patients undergoing elective colorectal surgery were identified over 6 months (N = 77), and their adherence to the ERAS protocol was assessed. Following the intervention of surgical resident and faculty education sessions on the ERAS protocol and the implementation of a standardized order set in the Electronic Medical Record, a postintervention cohort (N = 54) was selected for comparison over another 6 months. RESULTS: Among 77 patients who underwent elective colorectal surgery, the adherence rate to ERAS protocol was notably below 80% for most elements of the postoperative phase. When pre- and postintervention cohorts were compared, there were no significant differences in the baseline demographics and perioperative variables. After the implementation of our intervention, adherence rates were significantly improved in 7 out of 8 ERAS protocol elements of the postintervention phase. Among primary outcome measures, readmission rate (24.7% vs.9.4%; p = 0.022) and length of stay (7.3 ± 4.5 vs. 5.5 ± 3.6; p = 0.014) were significantly lower in the postintervention cohort. Although the rate of postoperative complications did not decrease significantly (33.8% vs. 31.5%; p = 0.284), there were fewer patients with postoperative ileus and surgical site infections. Outcomes were evaluated based on an 8-point score of postoperative ERAS elements. A significant decrease in mean length of stay and readmission rates is observed when at least 5 elements are completed, emphasizing the ERAS pathway's importance as a complementary bundle. CONCLUSION: Our study highlights the impact of resident education and electronic medical record standardization on ERAS adherence in colorectal surgery. This multidisciplinary approach improves adherence, reduces hospital stay, and enhances communication among healthcare providers for better patient outcomes.

The diagnostic conundrum in necrotizing otitis externa.

Necrotizing otitis externa (NOE) is an aggressive and fast-evolving infection of the external auditory canal. Late diagnoses and untreated cases can lead to severe, even fatal consequences and so early diagnosis and treatment are paramount. NOE is a notoriously challenging diagnosis to make. It is therefore important to understand what diagnostic modalities are available and how otolaryngologists can use them to accurately treat such an aggressive disease. This review aims to evaluate the different diagnostic options available in NOE and discuss their advantages and limitations, thus, providing an up-to-date picture of the multimodal approach required in the diagnosis of this disease.

Photo-conversion of CO2 using titanium dioxide: enhancements by plasmonic and co-catalytic nanoparticles.

Converting carbon dioxide (CO2) to hydrocarbons that can be used as fuels is beneficial from both environmental and economic points of view. In this study, nanoparticles are designed to enhance the photoreduction of CO2 on a titanium dioxide (TiO2) catalyst. An increase in catalytic activity is reported when silver (Ag), platinum (Pt) or bimetallic Ag-Pt and core-shell Ag@silica (SiO2) nanoparticles are used with the TiO2 semiconductor catalyst. Nanoparticles with different elemental composition or geometrical structure facilitate successive photo-excitation steps-generation, transport, storage and interfacial transfer of electrons and holes. Results show that while the addition of either type of nanoparticles augments product formation rates, bimetallic co-catalysts improve product selectivity. When both bimetallic co-catalysts and Ag@SiO2 nanoparticles are used in combination, product yields are enhanced more than seven fold in comparison to native TiO2 and high selectivity for methane (CH4) is observed. When the bimetallic Ag-Pt co-catalysts are tuned, a selectivity of CH4 of approximately 80%, as compared to 20% with only TiO2, can be achieved.

Tobacco use in Bollywood movies, tobacco promotional activities and their association with tobacco use among Indian adolescents.

BACKGROUND: Smoking in Hollywood movies is a known risk factor for teen smoking in the USA and Europe, but little is known about the association between exposure to tobacco use in Bollywood movies and teen tobacco use in India. METHODS: A cross-sectional sample of 3956 adolescents (eighth and ninth grades, ages 12-16 years) from 12 randomly selected New Delhi schools was surveyed in 2009, assessing tobacco use status, receptivity to tobacco promotions (based on owning or being willing to wear tobacco-branded merchandise) and exposure to tobacco use in movies. Quartiles of exposure to tobacco use in popular Bollywood movies released from 2006 to 2008 (n=59) were determined by content coding them for tobacco use and querying the adolescents whether they had seen each one. Logistic regression was used to control for covariates including age, gender, parent education, school performance, sensation-seeking propensity, family and peer tobacco use, and authoritative parenting. RESULTS: Altogether, the 59 movies contained 412 tobacco use occurrences. The prevalence of ever tobacco use among adolescents was 5.3%. Compared with low-exposure adolescents (quartile 1), the adjusted odds of ever tobacco use among high-exposure adolescents (quartile 4) was 2.3 (95% CI 1.3 to 3.9). Being receptive to tobacco promotions was also associated with higher adjusted odds of ever tobacco use, 2.0 (95% CI 1.4 to 3.0). CONCLUSION: Watching tobacco use in Bollywood movies and receptivity to tobacco promotional activities were both independently associated with ever tobacco use among adolescents in India, with ORs being similar to the studies of adolescents elsewhere.

Impact of tobacco advertisements on tobacco use among urban adolescents in India: results from a longitudinal study.

OBJECTIVES: To examine the longitudinal relationship between exposure and receptivity to tobacco advertisements and progression towards tobacco use among adolescents in India. DESIGN AND SETTING: A 2-year longitudinal group-randomised trial, Mobilizing Youth for Tobacco Related Initiatives (MYTRI), was undertaken from 2004 to 2006 in 32 schools in Delhi and Chennai. Among the control schools (n=16), mixed-effects regression models were used to assess the objectives. Subjects Students who were non-susceptible, never users of tobacco (n=2782) at baseline (2004) in the control schools of Project MYTRI, who progressed academically and were followed up at endline (2006). MAIN OUTCOME MEASURES: Progression towards tobacco use (on tobacco uptake continuum). RESULTS: Bivariate results suggest that exposure to tobacco advertisements at baseline was associated in a dose-dependent manner with progression at endline. Students exposed at more than four places were 1.5 times (95% CI 1.12 to 1.94; p<0.05) more likely to progress towards tobacco use at endline versus those not exposed. Among boys, those exposed at more than four places were 1.7 times more likely to progress (95% CI 1.14 to 2.62; p<0.05). These significant results disappeared in multivariate analysis, when other psychosocial risk factors for tobacco use were controlled. In both bivariate and multivariate analyses, the risk of progression at endline was more than two times higher (95% CI 1.28 to 4.32; p<0.05) among boys who were highly receptive versus non-receptive boys. The same relationship did not hold among girls. CONCLUSION: High receptivity to tobacco advertising predicts future progression to tobacco use among boys in India. Suggestive evidence exists of a causal relationship between tobacco marketing and adolescent tobacco use.

Association of breakfast intake with obesity, dietary and physical activity behavior among urban school-aged adolescents in Delhi, India: results of a cross-sectional study.

BACKGROUND: In developed countries, regular breakfast consumption is inversely associated with excess weight and directly associated with better dietary and improved physical activity behaviors. Our objective was to describe the frequency of breakfast consumption among school-going adolescents in Delhi and evaluate its association with overweight and obesity as well as other dietary, physical activity, and sedentary behaviors. DESIGN: Cross-sectional study. SETTING: Eight schools (Private and Government) of Delhi in the year 2006. PARTICIPANTS: 1814 students from 8th and 10th grades; response rate was 87.2%; 55% were 8th graders, 60% were boys and 52% attended Private schools. MAIN OUTCOME MEASURES: Body mass index, self-reported breakfast consumption, diet and physical activity related behaviors, and psychosocial factors. DATA ANALYSIS: Mixed effects regression models were employed, adjusting for age, gender, grade level and school type (SES). RESULTS: Significantly more Government school (lower SES) students consumed breakfast daily as compared to Private school (higher SES) students (73.8% vs. 66.3%; p<0.01). More 8th graders consumed breakfast daily vs.10th graders (72.3% vs. 67.0%; p<0.05). A dose-response relationship was observed such that overall prevalence of overweight and obesity among adolescents who consumed breakfast daily (14.6%) was significantly lower vs. those who only sometimes (15.2%) or never (22.9%) consumed breakfast (p<0.05 for trend). This relationship was statistically significant for boys (15.4 % vs. 16.5% vs. 26.0; p<0.05 for trend) but not for girls. Intake of dairy products, fruits and vegetables was 5.5 (95% CI 2.4-12.5), 1.7 (95% CI 1.1-2.5) and 2.2 (95% CI 1.3-3.5) times higher among those who consumed breakfast daily vs. those who never consumed breakfast. Breakfast consumption was associated with greater physical activity vs. those who never consumed breakfast. Positive values and beliefs about healthy eating; body image satisfaction; and positive peer and parental influence were positively associated with daily breakfast consumption, while depression was negatively associated. CONCLUSION: Daily breakfast consumption is associated with less overweight and obesity and with healthier dietary- and physical activity-related behaviors among urban Indian students. Although prospective studies should confirm the present results, intervention programs to prevent or treat childhood obesity in India should consider emphasizing regular breakfast consumption.

Ineffective pictorial health warnings on tobacco products: lessons learnt from India.

Pictorial warnings are effective in promoting smoking cessation as shown by research in the developed countries. This study aims to determine perceptions of Indians about the effectiveness of pictorial health warnings on tobacco packs which existed from May 31, 2009, to December 1, 2011. A cross-sectional survey was undertaken in five states of India with 1897 participants (56% males; 54% tobacco users). More tobacco users expressed that the pictorial warnings are inadequate to convey the health impact of tobacco use when compared with nonusers (71.50% vs. 62.75%; P < 0.001). More illiterates when compared with literates expressed their concern that the current pictorial warnings will not motivate them to quit (61.17% vs. 51.01%; P < 0.001). The new warnings implemented from December 1, 2011, in India are also not field-tested. Field testing and assessment of effectiveness of health warnings should be a mandatory requirement for Parties reporting on Article 11 of Framework Convention on Tobacco Control (FCTC).

Bisphosphonate-modified gold nanoparticles: a useful vehicle to study the treatment of osteonecrosis of the femoral head.

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that presents in children aged 2-14 years. To date, there is no effective medical therapy for treating LCPD largely due to an inability to modulate the repair process, including the predominance of bone resorption. This investigation aims to evaluate the feasibility of using gold nanoparticles (GNPs) that are surface modified with a bisphosphonate compound for the treatment of osteonecrosis at the cellular level. Studies have found osteoclast-mediated resorption to be a process that contributes significantly to the pathogenesis of femoral head deformities arising from Perthes disease. Our in vitro model was designed to elucidate the effect of alendronate-(a bisphosphonate) modified GNPs, on osteoclastogenesis and osteoclast function. RAW 264.7 macrophage cells were cultured with recombinant mouse receptor activator of NF-κB ligand (RANKL), which stimulates osteoclastogenesis, and were then treated with alendronate-modified GNPs for 24, 48, and 72 h. Cell proliferation, osteoclast function, and osteoclast morphology were evaluated by trypan blue dye exclusion assay, tartrate-resistant acid phosphatase (TRAP) staining, and transmission electron microscopy (TEM) imaging. Comparative studies were performed with GNPs that were only stabilized with citrate ions and with alendronate alone. Neither osteoclastogenesis nor osteoclast function were adversely affected by the presence of the citrate-GNP. Alendronate-modified GNPs had an enhanced effect on inducing osteoclast apoptosis and impairing osteoclast function when compared to unbound alendronate populations.

School policies, built environment and practices for non-communicable disease (NCD) prevention and control in schools of Delhi, India.

OBJECTIVE: To assess school policies, built environment and practices for prevention and control of non-communicable diseases in schools of Delhi, India. METHODS: School built environments and policies were assessed using a structured observation checklist in 10 private and 9 government schools which were randomly selected from all 184 co-educational schools with primary to senior secondary level education in Delhi, India. A self-administered questionnaire was also completed by teachers from each school (n = 19) to capture information specific to school policies. Surveys were also conducted with parent of students in class II (aged 6-7 years; n = 574) and student in class XI (aged 15-16 years, n = 755) to understand school practices. RESULTS: The majority of government (88.9%; n = 8) and private (80%; n = 8) schools reported having comprehensive school health policy. In terms of specific health behaviours, policies related to diet and nutrition in government schools were mostly restricted to primary levels with provision of the mid-day meal programme. All schools had two physical education periods per week of about 45-50 minutes. Most schools were compliant with tobacco-free school guidelines (n = 15 out of 19) and had alcohol control policies (n = 13 out of 19). Parent and student reports of practices indicated that school policies were not consistently implemented. CONCLUSION: Most schools in Delhi have policies that address health behaviours in students, but there was considerable variation in the types and number of policies and school environments. Government schools are more likely to have policies in place than private schools. Further work is needed to evaluate how these policies are implemented and to assess their impact on health outcomes.

Adolescent and adult perceptions of the effects of larger size graphic health warnings on conventional and plain tobacco packs in India: A community-based cross-sectional study.

INTRODUCTION: We studied adolescent and adult perceptions of the effects of larger size, 85% versus 40%, Graphic Health Warnings (GHWs) on conventional and plain tobacco packs, in India. METHODS: A cross-sectional survey was conducted with 2121 participants (aged ≥13 years), during the period 2015-16, in Delhi and Telangana, India. Four categories of GHWs on tobacco packs were shown: A - 40% existing (April 2013-April 2016), B - 40% new (April 2016-present), C - 85% new, and D - plain packs (85% new). Regression models tested percentage differences in choice of categories for eight outcomes, adjusted for gender, area of residence, socioeconomic status, age, and tobacco use. RESULTS: Of the total 2121 participants, 1120 were from Delhi, 1001 from Telangana, 50% were males, 62% were urban residents, 12% were adolescents, and 72% had never used tobacco. Among packs shown, the majority of participants perceived the 85% size GHWs more effective than the 40% size GHWs across all outcomes. The perceived increase in noticeability of GHWs was 45% for category C (p<0.05) and 43.5% for category D (p<0.05) versus category B. In Delhi, participants perceived plain packs to be most effective in motivating quitting, preventing initiation and conveying the health message. In Telangana, adolescents believed GHWs on plain packs were most noticeable, most effective for quitting and preventing initiation. CONCLUSIONS: The larger size 85% GHWs were perceived to be more effective in increasing noticeability of warnings, motivating cessation, preventing initiation, and conveying the intended health message. Support for plain packaging was higher in Delhi and among adolescents in Telangana.

Transcriptional control of viral gene therapy by cisplatin.

Ionizing radiation (IR) and radical oxygen intermediates (ROIs) activate the early growth response-1 (Egr1) promoter through specific cis-acting sequences termed CArG elements. Ad.Egr.TNF.11D, a replication-deficient adenoviral vector containing CArG elements cloned upstream of the cDNA for human recombinant TNF-alpha was used to treat human esophageal adenocarcinoma and rat colon adenocarcinoma cells in culture and as xenografts in athymic nude mice. Cisplatin, a commonly used chemotherapeutic agent, causes tumor cell death by producing DNA damage and generating ROIs. The present studies demonstrate induction of TNF-alpha production in tumor cells and xenografts treated with the combination of Ad.Egr.TNF.11D and cisplatin. The results show that the Egr1 promoter is induced by cisplatin and that this induction is mediated in part through the CArG elements. These studies also demonstrate an enhanced antitumor response without an increase in toxicity following treatment with Ad.Egr.TNF.11D and cisplatin, compared with either agent alone. Chemo-inducible cancer gene therapy thus provides a means to control transgene expression while enhancing the effectiveness of commonly used chemotherapeutic agents.

Formation and properties of composites based on microgels of a responsive polymer and TiO2 nanoparticles.

Organic-inorganic composites were prepared with titanium dioxide (TiO2) nanoparticles embedded within colloidal particles of a cross-linked, thermally responsive polymer. To promote the incorporation of unaggregated nanoparticles of TiO2, temperature responsive microspherical gels (microgels) of N-isopropylacrylamide (NIPAM) with interpenetrating (IP) linear chains of poly(acrylic acid) (PAAc) were synthesized. Dynamic light scattering (DLS) measurements revealed that these microgels reversibly shrink and swell in diameter from 300-400 nm to 600-800 nm with temperature. Two types of nanoparticles of TiO2 were immobilized within the IP-microgels-fine TiO2 nanoparticles synthesized by the hydrolysis of titanium(IV) isopropoxide and commercially available Degussa P25. Characterization of the composite was conducted using transmission electron microscopy (TEM) and UV-vis absorption spectroscopy from which it was determined that the extent of loading of the TiO2 within the colloidal particles can be easily manipulated from a low value of 10% (weight) to a value as high as 75%. The TiO2 nanoparticles were in a dispersed state within the microgels and the composites showed rapid (approximately minutes) sedimentation, which is useful for gravity separations. By using turbidometry to characterize the settling behavior of the organic-inorganic composites, it was found that the settling time decreases as the content of TiO2 increases within the particles.

Reversible aggregation of gold nanoparticles induced by pH dependent conformational transitions of a self-assembled polypeptide.

Controlling the stable structures of metallic nanoparticles on mesoscopic and macroscopic length scales is of great interest in nanotechnology. Here, this task is accomplished using a synthetic biopolymer that is responsive to external stimuli and undergoes changes in secondary structure. Reversible aggregation of gold nanoparticles (GNP) is induced by pH dependent changes in a self-assembled monolayer of disulfide modified poly(L-glutamic acid) (SSPLGA) with M(w) approximately 27000. The disulfide anchoring group drives chemisorption onto the gold nanoparticles and leads to the formation of a self-assembled monolayer. Characterization of the modified GNP and its aggregation behavior is performed using dynamic light scattering (DLS), UV-vis and IR spectroscopy, and transmission electron microscopy (TEM). Experimental results show that decrease in pH near 5.5 leads to aggregation of the modified GNP. The change in aggregation behavior with pH occurs within minutes, is reversible, and happens within a narrow range of pH from about 4.5 to 5.5. Comparison with literature data on molar enthalpy of hydrogen bonding, specific optical rotation, and ionization for the helix-coil transition of PLGA indicates that the aggregation of the SSPLGA modified GNP corresponds to the transition in the secondary structure of the polyacid.

A rapid spectrophotometric assay of some organophosphorus pesticide residues in vegetable samples.

A rapid and sensitive spectrophotometric method for the determination of some organophosphorus insecticides, i.e. malathion, dimethoate and phorate is described. It is based on the oxidation of organophosphorus pesticide with slight excess of N-bromosuccinimide (NBS) and the unconsumed NBS is determined with rhodamine B (lambda max: 550 nm). Beer's law is obeyed in the concentration range 0.108-1.08, 0.056-0.56 and 0.028-0.28 microg mL(-1) for malathion, phorate and dimethoate, respectively. The method has been successfully applied for the determination of organophosphorus pesticide residues in various vegetable samples.

Concentration-dependent effects of alendronate and pamidronate functionalized gold nanoparticles on osteoclast and osteoblast viability.

Severe osteoporotic diseases, such as Paget's disease, Osteogenesis Imperfecta, and Legg Calve Perthes disease, lack treatments that address the pathobiology of the diseases, as well as, long-term and prospective studies. Bisphosphonates, which are known to dramatically hinder the viability of osteoclast cells, along with gold nanoparticles (GNP) are a potential theranostic for osteoporotic diseases. We evaluated GNP functionalized with two different bisphosphonates, namely, alendronate and pamidronate. RANKL differentiated murine pre-osteoclasts (Raw 264.7) and murine osteoblasts (7F2) were treated with varying concentrations ranging from 0.1-5 µM of free and GNP bound bisphosphonates. GNPs with an average size of ∼15 nm were functionalized with alendronate and pamidronate through surface modification by self-assembly. MTT viability assay results show no changes in viability of the osteoclasts when treated with free bisphosphonates in the range of 1-5 µM, but significant decrease on treatment with functionalized GNP at concentrations above the range of 0.1-1 µM depending on the bisphosphonate. Osteoblast cell viability is maintained at all but the highest concentrations used. Qualitative and quantitative characterization by Western Blot for RANKL expression in the osteoblast cell line shows that expression is largely maintained. These results provide a basis for methods that use bisphosphonate functionalized GNP in the treatment of osteoporotic bone diseases. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 21-29, 2017.