Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells.

The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is that estrogen might protect against esophageal adenocarcinoma. Estrogen has previously been shown to stimulate apoptosis in esophageal squamous cancer cells. However, the effect of estrogen on esophageal adenocarcinoma cells has not been determined. We used immunoblotting analysis to determine the expression of estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki-67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen receptor modulator (SERM)-dependent effects on cell growth were determined by the CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin V/Propidium Iodide cell labeling and flow cytometry. We detected that physiological and supra-physiological concentrations of 17ß-estradiol and SERM decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus cells (QhTRT, ChTRT), decreased growth was also detected in response to estrogen/SERM. The level of estrogen receptor expression in the cell lines correlated with the level of anti-growth effects induced by the receptor agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a decrease in the expression of Ki-67 and an increase in E-cadherin expression in esophageal adenocarcinoma cells. This study suggests that esophageal adenocarcinoma and Barrett's esophagus cells respond to treatment with selective estrogen receptor ligands, resulting in decreased cell growth and apoptosis. Further research to explore potential therapeutic applications is warranted.

Antibiotic prescribing for upper respiratory tract infections in sarawak district hospitals.

Upper respiratory tract infection (URTI) is mostly viral in aetiology, but patients presenting with such complaints are frequently prescribed antibiotics. This may result in increased development of antimicrobial resistance. The objectives of this study are to determine the choice and proportion of oral antibiotics prescribed in patients with URTI, in a Sarawak district hospital setting. All outpatient prescriptions received in July 2011 in 10 hospitals with relevant diagnoses were analysed. A total of 6747 URTI prescriptions met the inclusion criteria, and 64.8% (95% CI 63.7%, 65.9%) had antibiotic prescribed. Medical Assistants (MAs) were significantly more likely to prescribe antibiotics compared to Medical Officers (MOs) (p < 0.001). Prescribers were significantly influenced by the patient's age and specific diagnosis when prescribing antibiotics for URTI (p < 0.001). Antibiotic choices differed between MOs and MAs, where some of the antibiotic choices were inappropriate. There is a need for multi-faceted interventions to improve antibiotic prescribing rate and choice.

Collegiate baseball pitchers demonstrate a relationship between ball velocity and elbow varus torque, both within and across pitchers.

High elbow varus torque during baseball pitching has been identified as a potential cause of ulnar collateral ligament injury in baseball pitchers. In general, elbow varus torque increases as ball velocity increases across pitchers. However, studies incorporating within-subject analyses report that not all professional pitchers have a positive relationship between elbow varus torque and ball velocity (T-V relationship). It remains unknown whether collegiate pitchers show the same trend as professionals in their T-V relationships. The current study investigated the T-V relationship of collegiate pitchers focusing on both across and within pitchers. Division 1 collegiate pitchers (n = 81) were assessed for elbow torque and ball velocity during pitching. Both across- and within-pitcher T-V relationships were significant (p < 0.05) using linear regression. However, more variance in elbow varus torque was explained using the within-pitcher relationship (R2 = 0.29) than the across-pitcher relationship (R2 = 0.05). Of the 81 pitchers, nearly half (n = 39) had significant T-V relationships, while the other half (n = 42) did not. Our findings indicate that the T-V relationship should be assessed on an individual basis as T-V is pitcher-specific.

Bilayer-mediated clustering and functional interaction of MscL channels.

Mechanosensitive channels allow bacteria to respond to osmotic stress by opening a nanometer-sized pore in the cellular membrane. Although the underlying mechanism has been thoroughly studied on the basis of individual channels, the behavior of channel ensembles has yet to be elucidated. This work reveals that mechanosensitive channels of large conductance (MscL) exhibit a tendency to spatially cluster, and demonstrates the functional relevance of clustering. We evaluated the spatial distribution of channels in a lipid bilayer using patch-clamp electrophysiology, fluorescence and atomic force microscopy, and neutron scattering and reflection techniques, coupled with mathematical modeling of the mechanics of a membrane crowded with proteins. The results indicate that MscL forms clusters under a wide range of conditions. MscL is closely packed within each cluster but is still active and mechanosensitive. However, the channel activity is modulated by the presence of neighboring proteins, indicating membrane-mediated protein-protein interactions. Collectively, these results suggest that MscL self-assembly into channel clusters plays an osmoregulatory functional role in the membrane.

A clinally varying promoter polymorphism associated with adaptive variation in wing size in Drosophila.

Body size often shows adaptive clines in many ectotherms across altitude and latitude, but little is known about the genetic basis of these adaptive clines. Here we identify a polymorphism in the Dca (Drosophila cold acclimation) gene in Drosophila melanogaster that influences wing size, affects wing:thorax allometry and also controls a substantial proportion of the clinal wing-size variation. A polymorphism in the promoter region of Dca had two common alleles showing strong reciprocal clinal variation in frequency with latitude along the east coast of Australia. The Dca-237 allele increased towards the tropics where wing size is smaller. A within-population association study highlighted that an increase in the frequency of this allele decreased wing size but did not influence thorax size. A manipulated increase in the level of expression of Dca achieved through UAS-GAL4 was associated with a decrease in wing size but had no effect on thorax size. This was consistent with higher Dca expression levels in family lines with higher frequency of the Dca-237 allele. Genetic variation in the promoter region of the Dca gene appears to influence adaptive size variation in the eastern Australian cline of Drosophila melanogaster and accounts for more than 10% of the genetic variation in size within and between populations.

Energy Management for Personalized Weight Reduction (EMPOWER) Program: Three-Year Outcome Data.

BACKGROUND: The current consensus guidelines for management of pediatric obesity recommend clinic-based, family-centered, multi-disciplinary interventions. It is well reported that these programs often only lead to modest improvements in BMI status. The individual factors that differentiate which patient's BMI status will improve vs. worsen remains understudied. A retrospective cohort study was conducted to evaluate the outcomes of EMPOWER clinic and identify the participant specific characteristics that predicted BMI status improvement in this population. METHODS: Youth who completed at least 6 visits in EMPOWER were included. Paired t-test was utilized to evaluate the mean change in zBMI, modified BMIz and %BMIp95 from baseline to 6th visit, and multivariate mixed effect models were utilized to analyze effect of baseline characteristics on change in BMI status. RESULTS: 92 participants were included in the analysis, 87% with severe obesity and 66% Hispanic. At the 6th visit, there was a significant reduction in zBMI (-0.09 SD, p <0.001) and modified BMIz (-0.0003 SD, p = 0.04) with a small reduction in %BMIp95 (-1.15 %, p = 0.20). Lower BMI status (p < 0.001) and absence of a comorbidity (p < 0.05) at baseline were predictors of BMI status improvement whereas age, gender, ethnicity, family history of obesity and insurance status were not significant predictors. CONCLUSIONS: Given that implementation of the current guidelines for management of obesity in pediatrics only results in modest BMI status reduction, further investigation is required to understand how the determinants of obesity-related health outcomes can guide development of more innovative, effective interventions for this high risk population.

An addiction model-based mobile health weight loss intervention in adolescents with obesity.

BACKGROUND: Clinical approaches to treating childhood obesity can be expensive and poorly reimbursed, and often produce suboptimal results. It has been theorized that overeating may have addictive qualities, and a sizable number of adolescents with obesity endorse addictive habits. Interestingly, few weight management interventions have tested techniques founded in addiction medicine principles. We therefore performed a pilot study of an addiction model based mHealth weight loss intervention in adolescents. METHODS: Adolescents with obesity were recruited from an multidisciplinary weight management clinic (EMPOWER). Adolescents without significant obesity comorbidities, who exhibited signs of addictive eating, based on the Yale Food Addiction Scale, were enrolled in a pilot study of an interactive, addiction-based, weight loss smartphone app with coaching (http://clinicaltrials.gov: NCT02689154). The app was designed to help subjects omit problem foods, avoid snacking and reduce meal size. A contemporary cohort of adolescents who completed the EMPOWER program were evaluated. Feasibility of recruitment, adherence, retention rates, BMI change and cost of intervention were examined. RESULTS: Eighteen participants were recruited to app intervention. App participants had higher retention (100% vs. 37%) and lower total cost per patient ($855.15 vs. $1428.00) than the EMPOWER clinic participants. App participants exhibited a significant decrease in zBMI and %BMIp95 over the 6 months (p < 0.001 and p = 0.001), which was comparable to the age-matched EMPOWER program completers (p = 0.31 and p = 0.06). CONCLUSIONS: An addiction medicine-based mHealth intervention targeted for adolescents was feasible to implement, resulted in high retention and adherence rates, and reduced zBMI and %BMIp95 in a more cost-effective manner than an in-clinic intervention.

Identification of candidate genes for fenvalerate resistance in Helicoverpa armigera using cDNA-AFLP.

A cDNA-amplified fragment length polymorphisms approach was undertaken to screen for candidate genes associated with fenvalerate resistance in the AN02 strain of Helicoverpa armigera. Larvae and adults of this strain manifest approximately 50-fold resistance, which is suppressible by piperonyl butoxide and controlled by the semidominant gene RFen1 previously mapped to AFLP Linkage Group 13. Two cytochrome P450s (CYP337B1 and CYP4S1), one carboxylesterase-like protein and one glutathione transferase were found to be constitutively upregulated in resistant insects. Mapping of these potential detoxification genes showed that one of them, the novel P450 CYP337B1, was tightly linked to the resistance locus. This suggests that the RFen1(R) allele has a cis-acting effect on CYP337B1 expression, and possible trans-acting effects on expression of other genes.

Is atropine needed with ketamine sedation? A prospective, randomised, double blind study.

OBJECTIVE: To compare atropine with placebo as an adjunct to ketamine sedation in children undergoing minor painful procedures. Outcome measures included hypersalivation, side effect profile, parental/patient satisfaction, and procedural success rate. METHODS: Children aged between 1 and 16 years of age requiring ketamine procedural sedation in a tertiary emergency department were randomised to receive 0.01 mg/kg of atropine or placebo. All received 4 mg/kg of intramuscular ketamine. Tolerance and sedation scores were recorded throughout the procedure. Side effects were recorded from the start of sedation until discharge. Parental and patient satisfaction scores were obtained at discharge and three to five days after the procedure, with the opportunity to report side effects encountered at home. RESULTS: A total of 83 patients aged 13 months to 14.5 years (median age 3.4 years) were enrolled over a 16 month period. Hypersalivation occurred in 11.4% of patients given atropine compared with 30.8% given placebo (odds ratio (OR) 0.29, 95% confidence interval (CI) 0.09 to 0.91). A transient rash was observed in 22.7% of the atropine group compared with 5.1% of the placebo group (OR 5.44, 95% CI 1.11 to 26.6). Vomiting during recovery occurred in 9.1% of atropine patients compared with 25.6% of placebo patients (OR 0.29, 95% CI 0.09 to 1.02). There was a trend towards better tolerance in the placebo group. No patient experienced serious side effects. CONCLUSION: Ketamine sedation was successful and well tolerated in all cases. The use of atropine as an adjunct for intramuscular ketamine sedation in children significantly reduces hypersalivation and may lower the incidence of post-procedural vomiting. Atropine is associated with a higher incidence of a transient rash. No serious adverse events were noted.

House Dust Mites in Human ear.

A study was carried out to investigate the presence of mites in human ear in 58 patients (113 ears). Ear scrapings were examined under the microscope by a parasitologist for the presence of house dust mites. Results showed the presence of house dust mites in 8 (7.1%) ears. We can conclude that mites are normal commensals of the external ears in tropical countries.

Association between antenatal cytokine production and the development of atopy and asthma at age 6 years.

BACKGROUND: Various lines of evidence suggest that antenatal factors are important in determining susceptibility to atopy and asthma. One possible mechanism is cytokines, production of which in the placenta is high throughout gestation and which protect placental integrity via control of local immunological homoeostasis. We investigated antenatal cytokine concentrations in a prospective birth cohort, intensively monitored for atopy and asthma outcomes at age 6 years. METHODS: Cryopreserved cord-blood serum samples from 407 children were assayed for interleukins 4, 5, 6, 10, 12, and 13, interferon gamma, and tumour necrosis factor alpha (TNFalpha). Associations between family, antenatal, and perinatal factors, cord-blood cytokine concentrations, and atopy or asthma outcomes were analysed by logistic regression. Causal effects of cytokines on outcomes were estimated by propensity scores based on family, antenatal, and perinatal factors. FINDINGS: Detectable cord-blood concentrations of interleukin 4 and interferon gamma were each associated with lower risk of physician-diagnosed asthma (adjusted odds ratios 0.60 [95% CI 0.37-0.99] and 0.60 [0.37-0.97] respectively), current asthma (0.59 [0.33-1.00] and 0.39 [0.22-0.71]), and current wheeze (0.55 [0.32-0.93] and 0.52 [0.31-0.90]) and atopy (sensitisation to some inhalant allergens) outcomes at 6 years. High concentrations of TNFalpha were associated with lower risk of atopy but not with asthma risk. These associations were broadly unaltered by propensity-score adjustment. Maternal smoking was associated with higher risk of both wheeze at 6 years and lower concentrations of interleukin 4 and interferon gamma in cord blood. INTERPRETATION: The mechanism underlying attenuated T-helper-1/T-helper-2 cytokine production in high-risk children also apparently operates in control of cytokine production in the fetoplacental unit. The finding that this mechanism is dysregulated by maternal smoking suggests it is a target for antenatal environmental factors relevant to asthma aetiology.

Relationship between smoking and weight control efforts among adults in the united states.

BACKGROUND: The effect of weight control concerns on smoking among adults is unclear. We examined the association between smoking behavior and weight control efforts among US adults. METHODS: A total of 17 317 adults responded to the Year 2000 Supplement of the 1995 National Health Interview Survey (83% combined response rate). Respondents provided sociodemographic and health information, including their smoking history and whether they were trying to lose weight, maintain weight, or gain weight. RESULTS: Rates of smoking were lower among adults who were trying to lose or maintain weight than among those not trying to control weight (25% vs 31%; P<.001). After adjustment for sex, race, education, income, marital status, region of the country, and body mass index, the relationship between trying to lose weight and current smoking varied according to age. Among adults younger than 30 years, those trying to lose weight were more likely to smoke currently (odds ratio, 1.36 [95% confidence interval, 1.09-1.70]), whereas older adults trying to lose weight were as likely or less likely to smoke compared with adults not trying to control weight. After adjustment, smokers of all ages who were trying to lose weight were more likely to express a desire to quit smoking. Results were similar after stratification by sex and body mass index. CONCLUSIONS: Adults younger than 30 years are more likely to smoke if they are trying to lose weight. However, smokers of all ages who are trying to lose weight are more likely to want to stop smoking. Patients' weight control efforts should not discourage clinicians from counseling about smoking cessation. Education about smoking and healthy weight control methods should target young adults.

Bleeding following coblation tonsillectomy: a 10-year, single-surgeon audit and modified grading system.

OBJECTIVE: Coblation tonsillectomy can be controversial. This study assessed post-tonsillectomy haemorrhage outcomes for patients operated on by a single experienced coblation-trained ENT surgeon. STUDY DESIGN: A retrospective audit of coblation tonsillectomies was performed using the Flinders modification of Stammberger criteria for post-tonsillectomy haemorrhage. METHOD: Case note review, interview and database interrogation were utilised to obtain the dataset. Haemorrhage results were compared to reports in the current literature. RESULTS: Of those who underwent coblation tonsillectomy, 3.4 per cent were readmitted to hospital with haemorrhage and 1.3 per cent returned to the operating theatre (0.4 per cent primary haemorrhage and 0.9 per cent secondary haemorrhage). Younger children had a lower risk of returning to the operating theatre than older children or adults (0.3 per cent under the age of 12 years vs 2.0 per cent aged 12 years or older). CONCLUSION: Coblation can be a safe method for tonsillectomy with low complication rates when performed by an experienced ENT surgeon. The Flinders modification of the Stammberger criteria for post-tonsillectomy haemorrhage provides a simple system for data comparison.

Promoter analysis of the murine T-cell protein tyrosine phosphatase gene.

The T-cell protein tyrosine phosphatase (TC PTP) is expressed ubiquitously at all stages of mammalian development. However, mRNA levels fluctuate in a cell-cycle-dependent manner, reaching peak levels in late G1, and rapidly decreasing in S phase. Furthermore, TC PTP being present in higher amounts in lymphoid tissues, we have recently shown that it is essential for proper maintenance of both the bone marrow micro-environment and B- and T-cell functions. In order to better understand the elements controlling the expression pattern of this gene, we have isolated and characterized approx. 4kb of the murine TC PTP promoter. DNA sequencing of the proximal 5' region revealed the absence of both TATAA and CAAT boxes. Primer extension analysis and S1 nuclease mapping techniques identified multiple transcription initiation sites. Functional promoter activity was determined using transfection experiments of promoter deletion constructs fused to a CAT reporter construct. Our results indicate that the minimal promoter sequence required for functional expression is contained within the first 147bp of the TC PTP promoter. In addition, consistent with the cell-cycle-dependent expression of TC PTP, we localized a domain between 492 and 1976bp from the transcription initiation site through which repression occurs. In conclusion, although initiator-driven transcription allows for ubiquitous expression of TC PTP, we define general transcription motifs present within the promoter that may mediate specific modulations of the TC PTP gene.

Influence of financial productivity incentives on the use of preventive care.

PURPOSE: We examined whether physician factors, particularly financial productivity incentives, affect the provision of preventive care. SUBJECTS AND METHODS: We surveyed and reviewed the charts of 4,473 patients who saw 1 of 169 internists from 11 academically affiliated primary care practices in Boston. We abstracted cancer risk factors, comorbid conditions, and the dates of the last Papanicolaou (Pap) smear, mammogram, cholesterol screening, and influenza vaccination. We obtained physician information including the method of financial compensation through a mailed physician survey. We used multivariable logistic regression to examine the association between physician factors and four outcomes based on Health Plan Employer Data and Information Set (HEDIS) measures: (1) Pap smear within the prior 3 years among women 20 to 75 years old; (2) mammogram in the prior 2 years among women 52 to 69 years old; (3) cholesterol screening within the prior 5 years among patients 40 to 64 years old; and (4) influenza vaccination among patients 65 years old and older. All analyses accounted for clus-tering by provider and site and were converted into adjusted rates. RESULTS: After adjustment for practice site, clinical, and physician factors, patients cared for by physicians with financial productivity incentives were significantly less likely than those cared for by physicians without this incentive to receive Pap smears (rate difference, 12%; 95% confidence interval [CI]: 5% to 18%) and cholesterol screening (rate difference, 4%; 95% CI: 0% to 8%). Financial incentives were not significantly associated with rates of mammography (rate difference, -3%; 95% CI: -15% to 10%) or influenza vaccination (rate difference, -13%; 95% CI: -28% to 2%). CONCLUSIONS: Our findings suggest that some financial productivity incentives may discourage the performance of certain forms of preventive care, specifically Pap smears and cholesterol screening. More studies are needed to examine the effects of financial incentives on the quality of care, and to examine whether quality improvement interventions or incentives based on quality improve the performance of preventive care.

Kinetics and metabolism of 11-deoxycortisol in a patient with congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency.

The kinetic features of 11-deoxycortisol (S) were studied in a 11 beta-hydroxylase deficient boy. After i.v. administration of 35 kBq [3H]S (11 pmol) together with 44 nmol [13C]cortisol all his urine was collected during the next 3 days. A recently reported kinetic model, by which the fate of radioactive cortisol (F) in the body can be described by analysis of only the urinary radioactivity, has been used to calculate the rate constants of S metabolism. The overall half-life of S in the circulation was 4.7 min, which is very close to a reported half-live of the rapid phase: 4.1 min determined from the plasma radioactivity. The time of maximal accumulation of S in the first metabolic pool--26 min is about one quarter of that found for F--109 +/- 20 min (n = 8). The half-live of the S metabolites in the body was 7.0 h, equal to that of F: 6.1 +/- 0.9 h (n = 8). Obviously S is taken up into the metabolic organs 4 times faster than F, but it is not metabolized faster. The production rates of S and F were 127 and 2.1 mumol/(m2*d), respectively, pointing to a severely deficient synthesis of F. However, from the urinary excretion of 3 alpha,21-dihydroxy-5 beta-pregnan-20-one in relation to 3 alpha,11 beta,21-trihydroxy-5 beta-pregnan-20-one it cannot be concluded that the synthesis of corticosterone was strongly impaired.

Immunology of renal transplantation in Singapore.

Renal transplantation is the best form of renal replacement therapy for patients suffering from endstage renal failure. While correcting the metabolic consequences of uremia, it is the only form of replacement therapy which permits full rehabilitation of the patient. However, the successful engraftment of a renal allograft is frequently limited by immunologically mediated graft loss which can be as high as 50% in the first year in cadaveric transplants. Since the beginning of the history of transplantation, various methods of modifying allograft rejection, both pretransplantation and posttransplantation have been studied. In this paper, we report the pretransplantation immunological factors that appear to modulate graft survival in renal transplantation in Singapore.

House Dust Mites in Human ear

A study was carried out to investigate the presence of mites in human ear in 58 patients (113 ears). Ear scrapings were examined under the microscope by a parasitologist for the presence of house dust mites. Results showed the presence of house dust mites in 8 (7.1%) ears. We can conclude that mites are normal commensals of the external ears in tropical countries.

Selection for cold resistance alters gene transcript levels in Drosophila melanogaster.

Microarrays have been used to examine changes in gene expression underlying responses to selection for increased stress resistance in Drosophila melanogaster, but changes in expression patterns associated with increased resistance to cold stress have not been previously reported. Here we describe such changes in basal expression levels in replicate lines following selection for increased resistance to chill coma stress. We found significant up- or down-regulation of expression in 94 genes on the Affymetrix Genome 2.0 array. Quantitative RT-PCR was used to confirm changes in expression of six genes. Some of the identified genes had previously been associated with stress resistance but no previously identified candidate genes for cold resistance showed altered patterns of expression. Seven differentially expressed genes that form a tight chromosomal cluster and an unlinked gene AnnX may be potentially important for cold adaptation in natural populations. Artificial selection for chill coma resistance therefore altered basal patterns of gene expression, but we failed to link these changes to plastic changes in expression under cold stress or to previously identified candidate genes for components of cold resistance.