The clinical pattern of HER-2/neu oncogene overexpressing breast cancer in Pakistani patients at initial presentation: an analysis of HER-2/neu positive versus negative disease--a preliminary report

Background: HER 2/new oncogene is an important prognostic marker in Breast Cancer and has implications in therapy planning.Objective: To describe the clinical features of HER 2/new positive and negative Breast Cancer in the Pakistani patient population and note clinical differences between the two groups if any.Design: A retrospective analysis of Breast Cancer cases at the Aga Khan University, Hospital.METHOD: Immunochemical staining on formation fixed paraffin embedded tissue using oxidase antiperoxidase method. A total of 152 Breast cancer tissue samples were tested for HER-2/neu gene presence. Of these 43 (39%) samples tested positive and 109 (61%) tested negative. A comparison of the two groups revealed that only a few factors tested for either significance or borderline statistical significance between the two groups. These factors included the estrogen receptor status and the number of lymph nodes involved in the axilla. The progesterone receptor status was of borderline significance.CONCLUSION: Given the large number of factors tested it appears that there is no consistent defining feature which helps to separate HER-2/neu positive versus HER-2/neu negative cases with Breast Cancer

Impedance-Based Water-Quality Monitoring Using the Parallel-Plate Method

The application of electromagnetic (EM) waves to measure the electrical properties (dielectric constant and loss tangent) of materials is a well-known approach. The electrical properties can be used to indirectly measure several physical properties of solutions in water such as the concentration and chemical composition of contaminants in water, as a representative of the liquid phase in soil. A capacitive method of measuring dielectric properties of solutions is proposed to detect and determine low-concentration chemical and biological contaminations in water. The primary objective of this project is to design a low-cost sensor that would require small volumes of samples to detect low concentrations of dissolved contaminants in water. A forward model was developed using a finite-element method (FEM) to simulate the experimental setup (EXP). A calibration function was also developed to minimize deviations between FEM and EXP results for benchmark/reference solutions with known dielectric properties. The validated, calibrated forward model was then inverted to calculate the electrical properties of unknown solutions using the corresponding EXP results

Relative validity of a food and beverage preference questionnaire to characterize taste phenotypes in children adolescents and adults

To assess the relative validity of our food and beverage preference questionnaire we investigated the association between sweet and fatty taste preference scores (assessed using a food and beverage preference questionnaire) and sweet and fatty food propensity scores (derived from a food frequency questionnaire). In I.Family, a large European multi-country cohort study, 12, 207 participants from Cyprus, Estonia, Germany, Hungary, Italy, Spain and Sweden, including 5291 adults, 3082 adolescents, and 3834 children, completed a food and beverage preference questionnaire with 63 items. Cumulative preference scores for sweet and fatty taste were calculated from the single item ranking ranging from 1 to 5. The relative consumption frequency of foods classified as sweet and fatty was used to calculate the corresponding consumption propensities, a continuous variable ranging from 0 to 100. We conducted regression analyses to investigate the association between sweet and fatty taste preference scores and sweet and fatty food propensity scores, respectively, separately for adults, adolescents =12 years, and for children <12 years. The overall sweet taste preference score was positively associated with the sweet food consumption propensity score (ß = 2.4, 95% CI: 2.1;2.7) and the fatty taste preference score was positively associated with the fatty food consumption propensity score (ß = 2.0, 95% CI: 1.8;2.2). After stratification for age (children <12 years, adolescents =12 years, and adults), the effect remained significant in all age groups and was strongest in adolescents and adults. We conclude that our food and beverage preference questionnaire is a useful instrument for epidemiological studies on sensory perception and health outcomes and for the characterization of sensory taste phenotypes

Male form of persistent Mullerian duct syndrome type I (hernia uteri inguinalis) presenting as an obstructed inguinal hernia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Persistent Mullerian duct syndrome is a rare form of male pseudo-hermaphroditism characterized by the presence of Mullerian duct structures in an otherwise phenotypically, as well as genotypically, normal man; only a few cases have been reported in the worldwide literature. We report the case of a 30-year-old man with unilateral cryptorchidism on the right side and a left-sided obstructed inguinal hernia containing a uterus and fallopian tube (that is, hernia uteri inguinalis; type I male form of persistent Mullerian duct syndrome) coincidentally detected during an operation for an obstructed left inguinal hernia.</p> <p>Case presentation</p> <p>A 30-year-old South Indian man was admitted to our facility with a left-sided obstructed inguinal hernia of one day's duration. He had a 12-year history of inguinal swelling and an absence of the right testis since birth. Our patient had well developed masculine features. Local physical examination revealed a left-sided obstructed inguinal hernia with an absence of the right testis in the scrotum. Exploration of the inguinal canal revealed an indirect inguinal hernia containing omentum, the left corner of the uterus and a left fallopian tube. Extension of the incision revealed a well formed uterus, cervix and upper part of the vagina attached to the prostate by a thick fibrosed band. Total excision of the uterus, bilateral fallopian tubes and right testis was performed. A biopsy was taken from the left testis. The operation was completed by left inguinal herniorraphy. Histopathological examination of the hernial contents was consistent with that of a uterus and fallopian tubes without ovaries. Both testes were atrophied, with complete arrest of spermatogenesis. Post-operative karyotype analyses were negative for 46,XY and Barr bodies on buccal smear. A semen examination revealed azoospermia with a low serum testosterone level.</p> <p>Conclusions</p> <p>In cases of unilateral or bilateral cryptorchidism associated with inguinal hernia, as in our patient's case, the possibility of persistent Mullerian duct syndrome should be kept in mind in order to prevent further complications such as infertility and malignant change. Hernia uteri inguinalis is the type I male form of persistent Mullerian duct syndrome, characterized by one descended testis and herniation of the ipsilateral corner of the uterus and fallopian tube into the inguinal canal.</p

Independent mechanisms of stimulation of polynucleotide kinase/phosphatase by phosphorylated and non-phosphorylated XRCC1

XRCC1 plays a central role in mammalian single-strand break repair. Although it has no enzymatic activity of its own, it stimulates the activities of polynucleotide kinase/phosphatase (PNKP), and this function is enhanced by protein kinase CK2 mediated phosphorylation of XRCC1. We have previously shown that non-phosphorylated XRCC1 stimulates the kinase activity of PNKP by increasing the turnover of PNKP. Here we extend our analysis of the XRCC1-PNKP interaction taking into account the phosphorylation of XRCC1. We demonstrate that phosphorylated and non-phosphorylated XRCC1 interact with different regions of PNKP. Phosphorylated XRCC1 binds with high affinity (Kd = 3.5 nM and 1 : 1 stoichiometry) to the forkhead associated (FHA) domain, while non-phosphorylated XRCC1 binds to the catalytic domain of PNKP with lower affinity (Kd = 43.0 nM and 1 : 1 stoichiometry). Under conditions of limited enzyme concentration both forms of XRCC1 enhance the activities of PNKP, but the effect is more pronounced with phosphorylated XRCC1, particularly for the kinase activity of PNKP. The stimulatory effect of phosphorylated XRCC1 on PNKP can be totally inhibited by the presence of excess FHA domain polypeptide, but non-phosphorylated XRCC1 is not susceptible to competition by the FHA domain. Thus, XRCC1 can stimulate PNKP by two independent mechanisms

Association analysis of Neuregulin 1 candidate regions in schizophrenia and bipolar disorder

Schizophrenia (SCZ) and bipolar disorder (BPD) are severe heritable psychiatric disorders involving a complex genetic aetiology. Neuregulin 1 (NRG1) is a leading candidate gene for SCZ, and has recently been implicated in BPD. We previously reported association of two NRG1 haplotypes with SCZ and BPD in a Scottish case–control sample. One haplotype is located at the 5′ end of the gene (region A), and the other is located at the 3′ end (region B). Here, association to haplotypes within regions A and B was assessed in patients with SCZ and BPD in a second Scottish case–control sample and in the two Scottish samples combined. Association to region B was also assessed in patients with SCZ and BPD in a German case–control sample, and in all three samples combined. No evidence was found for association in the new samples when analysed individually; however, in the joint analysis of the two Scottish samples, a region B haplotype comprising two SNPs (rs6988339 and rs3757930) was associated with SCZ and the combined case group (SCZ: p = 0.0037, OR = 1.3, 95% CI: 1.1–1.6; BPD + SCZ: p = 0.0080, OR = 1.2, 95% CI: 1.1–1.5), with these associations withstanding multiple testing correction at the single-test level (SCZ: pst = 0.022; BPD + SCZ: pst = 0.044). This study supports the involvement of NRG1 variants in the less well studied 3′ region in conferring susceptibility to SCZ and BPD in the Scottish population

Factors predicting pain and early discontinuation of tumour necrosis factor-α-inhibitors in people with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register

Background: We examined pain levels in 2 cohorts assembled from the British Society for Rheumatology Biologics Register (BSRBR), and investigated which factors predicted Bodily Pain scores and discontinuation of TNFα-inhibitors. Method: Data were retrieved from BSRBR-RA databases for up to 1 year after commencing TNFα-inhibitors (n=11995) or being treated with non-biologic therapies (n=3632). Bodily Pain scores were derived from the Short Form-36 (SF36) questionnaire and norm-transformed to allow comparison with UK population averages. Discontinuation data were from physician reports. Other data, including 28-joint disease activity score (DAS28) measurements, were from clinical examination, interview, medical records and self-report questionnaires. DAS28-P was derived as the proportion of DAS28 attributed to patient-reported factors (tender joint count and visual analogue score). Missing baseline variables from both cohorts were imputed into 20 replicate datasets. Odds ratios (OR) and adjusted OR were calculated for higher than median pain within each cohort. Results: Participants reported moderate to severe pain at baseline, and pain scores remained >1SD worse than normal population standards at 1 year, even when disease activity responded to treatment. Baseline pain was associated with DAS28-P, worse physical function, worse mental health, and DAS28. After logistic regression, independent predictors of higher than median pain at follow up were baseline Bodily Pain score, higher DAS28-P, worse physical function or mental health and co-morbidities. Higher age, male gender, and higher BMI were additional independent predictors of higher pain in participants who received TNFα-inhibitors. Baseline pain was also one of the predictors of discontinuation of the first TNFα-inhibitor within 1 year, as were female gender, current smoking, co-morbidities, extra-articular manifestations and worse function. Conclusion: Pain persists in people with treated RA, even in those for whom inflammation responds to treatment. Worse pain outcomes are predicted by factors different to those typically found to predict inflammatory disease activity in other studies. Worse pain at baseline also predicts discontinuation of TNFα-inhibitors. Improved pain management should complement inflammatory disease suppression in RA