Chemical Changes in Amniotic Fluid

An ever present dilemma in modern obstetrical management is the proper timing of delivery of the fetus in situations where complications either threaten its own life in utero or significantly affect maternal morbidity. In such situations the obstetrician is confronted with the equivocal choice between premature delivery and the high risk to the fetus of continued intrauterine existence. In addition, he is placed in a unique position where any sort of direct communication with one of his patients, namely the fetus, is nearly impossible. In the past, the delivery of obstetrical care to the fetus and the monitoring of its well-being were possible only through the agency of the maternal organism. To improve upon this situation, methods had to be found that would give a more direct and accurate reflection of fetal status. Hence, as complete a collection as possible of accurate indices relating to the fetal maturity is of great importance to the obstetrician. Some of the notable complications of pregnancy in which these indices would be of value are diabetes, toxemia, erythroblastosis fetalis, and previous poor obstetrical history: for example, cases requiring repeat cesarean sections or abruptio placentae

The discovery and mechanism of action of letrozole

Because estrogen contributes to the promotion and progression of breast cancer, a greater understanding of the role of estrogen in breast cancer has led to therapeutic strategies targeting estrogen synthesis, the estrogen receptor, and intracellular signaling pathways. The enzyme aromatase catalyses the final step in estrogen biosynthesis and was identified as an attractive target for selective inhibition. Modern third-generation aromatase inhibitors (AIs) effectively block the production of estrogen without exerting effects on other steroidogenic pathways. The discovery of letrozole (Femara®) achieved the goal of discovering a highly potent and totally selective AI. Letrozole has greater potency than other AIs, including anastrozole, exemestane, formestane, and aminoglutethimide. Moreover, letrozole produces near complete inhibition of aromatase in peripheral tissues and is associated with greater suppression of estrogen than is achieved with other AIs. The potent anti-tumor effects of letrozole were demonstrated in several animal models. Studies with MCF-7Ca xenografts successfully predicted that letrozole would be clinically superior to the previous gold standard tamoxifen and also indicated that it may be more effective than other AIs. An extensive program of randomized clinical trials has demonstrated the clinical benefits of letrozole across the spectrum of hormone-responsive breast cancer in postmenopausal women

Attitudes of Secondary Regular School Teachers Toward Inclusive Education in New Delhi, India: A Qualitative Study

This study aimed to identify the attitudes of regular school teachers in Delhi, India, toward the inclusion of students with disabilities. It also explored their views regarding facilitators of inclusive education. Respondents were secondary school teachers working in schools in Delhi that implement inclusive education for students with disabilities. Two focus group interviews with ten participants in each group and 20 individual semi-structured interviews were conducted. The flexible qualitative analysis program QRS NVivo was utilized for data analysis. The major finding of the study was that the teachers held positive attitudes toward the inclusion of students with disabilities. The teachers also suggested a number of facilitators of inclusion in their schools such as improved infrastructure, policy changes, and provisions for institutional resources

A Conceptual Framework to Predict Mental Health Patients' Zoning Classification.

Zoning classification is a rating mechanism, which uses a three-tier color coding to indicate perceived risk from the patients' conditions. It is a widely adopted manual system used across mental health settings, however it is time consuming and costly. We propose to automate classification, by adopting a hybrid approach, which combines Temporal Abstraction to capture the temporal relationship between symptoms and patients' behaviors, Natural Language Processing to quantify statistical information from patient notes, and Supervised Machine Learning Models to make a final prediction of zoning classification for mental health patients

Inhibitors of oestrogen biosynthesis: preclinical studies with CGS 16949A, a new nonsteroidal aromatase inhibitor

Inhibitors of the aromatase enzyme represent a class of therapeutic agents which potently inhibit oestrogen biosynthesis in vivo. This inhibition of oestrogen biosynthesis is well established as effective therapy in the treatment of oestrogen-dependent breast cancer. CGS 16949A [4-(5,6,7,8-tetrahydroimidazo-[l,5-a]pyridin-5-yl)-benzonitrile hydrochloride] is a non-steroidal imidazole derivative which is a potent competitive aromatase inhibitor in vitro. At a maximally effective concentration, it selectively inhibits aromatase and does not affect glucocorticoid production from the adrenal in vitro. In vivo in the rat, CGS 16949A effectively reduces ovarian oestrogen content and potently inhibits an aromatase-mediated androgen-induced uterine hypertrophy. Oral treatment of adult, cyclic female rats with CGS 16949A disrupts cyclicity, inhibits ovulation, reduces uterine weight and suppresses serum oestradiol, all expected sequelae of oestrogen deprivation. At maximally effective doses, there is no evidence of adrenal hypertrophy, indicating that adrenal steroidogenesis is unaffected. In the DMBA-induced mammary carcinoma model in the rat, CGS 16949A caused almost complete regression of palpable tumours and significantly suppressed the appearance of new tumours at a maximally effective oral dose. Thus, CGS 16949A is a potent and selective inhibitor of the aromatase enzyme. In the rat, it is very efficacious in inhibiting oestrogen biosynthesis and in suppressing the growth of DMBA-induced mammary tumour

Circular Patch Antenna with Defected Ground for UWB Communication with WLAN Band Rejection

The design and performance of coplanar waveguide fed modified circular patch antenna for possible application in ultra wideband communication systems with band rejection for upper wireless local area network band (5.15 GHz - 5.85 GHz) is reported. This antenna is designed on glass epoxy FR4 substrate having size 30 mm × 20 mm × 1.59 mm. The coplanar waveguide fed circular patch antenna is modified by introducing L shaped slits in ground plane and U shaped slot in patch and performance analysis of antenna is simulated by applying CST microwave studio simulation software. Different designed antennas were tested with available experimental facilities. The developed end product shows a nice matching with feed network at frequencies 2.62 GHz, 3.94 GHz and 8.50 GHz and provides 10.38 GHz (3.33 GHz - 13.71 GHz) impedance bandwidth with wireless local area network 5.5 GHz (4.74 GHz - 6.15 GHz) band rejection. The co and cross polar patterns in elevation and azimuth planes at two frequencies namely 2.62 GHz and 3.94 GHz are obtained which dictate that co-polar patterns are significantly better than cross polar patterns. The simulated peak gain of antenna is close to 3.86 dBi and gain variation with frequency shows a sharp gain decrease in the frequency range 4.74 GHz to 6.15 GHz.

Effect of long-term treatment with aromatase inhibitor on testicular function of adult male bonnet monkeys (M. radiata)

The role/need for estrogen in regulating testicular function of adult male bonnet monkeys (M. radiata) has been investigated by dosing orally a group of five normal males 2.5 mgs of CGP 47645, a long-acting nonsteroidal aromatase inhibitor (AI), once every 5 days for over 150 days. Such treatment resulted in a 10-fold increment in nocturnal serum testosterone (T) levels, which were sustained for 85 days of treatment, and a twofold increment in basal serum T levels was present throughout the 150 days of treatment. Analysis of ejaculated semen showed a marked reduction (~90%) in sperm counts in four out of five monkeys between Days 55-85 of treatment. During this period, the motility score also was markedly reduced from a normal score of 3-5 to 0-2. Flow cytometric analysis of testicular germ cells obtained from biopsy tissue taken on Days 63 and 120 indicated a marked reduction only in elongating/elongated spermatid population (compared to Day 0 values), suggesting inhibition in spermiogenic process. Epididymal sperm maturation also seemed effected as sperm chromatin, on flow cytometric analysis for decondensability following exposure to 5 mM dithiotreitol, showed to be in a hypercondensed state. This study thus indicates that estrogen has an important role in providing normal testicular and sperm function in the primate

Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics

BACKGROUND: Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor–positive (ER+) breast cancer. METHODS: Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response. Cox proportional hazards were used to identify factors associated with relapse-free survival (RFS) and breast cancer–specific survival (BCSS) in 158 women. A preoperative endocrine prognostic index (PEPI) for RFS was developed from these data and validated in an independent study of 203 postmenopausal women in the IMPACT trial, which compared treatment with anastrozole, tamoxifen, or the combination 3 months before surgery. Statistical tests were two-sided. RESULTS: Median follow-up in P024 was 61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with higher stages, P < .001). Multivariable testing of posttreatment tumor characteristics revealed that pathological tumor size, node status, Ki67 level, and ER status were independently associated with both RFS and BCSS. The PEPI model based on these factors predicted RFS in the IMPACT trial (P = .002). CONCLUSIONS: Breast cancer patients with pathological stage 1 or 0 disease after neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical specimen (PEPI score 0) have an extremely low risk of relapse and are therefore unlikely to benefit from adjuvant chemotherapy