Duavee: a tissue-selective estrogen complex for menopausal symptoms and prevention of osteoporosis

Post-menopausal women suffer from a plethora of problems like vasomotor symptoms, vulvovaginal atrophy (VVA), bone loss, and all this can be attributed to estrogen deficiency. The conventional treatment till date for these hormone deficient manifestations have been estrogen replacement therapy in hysterectomized female or a combination of estrogen and progesterone therapy in women with an intact uterus. The reason for adding progesterone is to protect the endometrium from estrogenic stimulation. The drawback with the combination therapy was irregular vaginal bleeding and breast discomfort, which led to the discontinuation of this therapy. The United States Food and Drug Administration, has recently approved a novel tissue selective estrogen complex comprising of conjugated estrogen (0.45 mg) and a selective estrogen receptor modulator, bazedoxifene (BZA) (20 mg) for the treatment of moderate to severe vasomotor symptoms and prevention of osteoporosis in non-hysterectomized post-menopausal women. This combination retains the benefits of estrogen on vasomotor symptoms, VVA and bone density along with the protective effect of BZA on endometrium and breast tissue. The results of clinical trials have been promising but what still needs to be evaluated is the long term safety of this pair on venous thromboembolism, stroke, and breast cancer

Linaclotide: a guanylate cyclase agonist for treatment of irritable bowel syndrome with constipation and chronic constipation in adults

Linaclotide, a 14 aminoacid peptide is an intestinal secretagogue and works by stimulating guanylate cyclase (GC-C) present in the intestinal epithelium, which leads to improvement in symptoms of irritable bowel syndrome with constipation and chronic constipation in adults. Treatments available currently for these gastrointestinal problems have not been very satisfactory and many new options are therefore being explored to provide relief to these patients. Linaclotide has shown promising results in various clinical trials and hence was approved by US Food and Drug Administration (FDA) in 2012

Operational Flexibility and Market Valuation of Earnings

This paper examines the association between the stock returns and accounting earnings of firms that have different levels of operational flexibility. Operational flexibility is a firm\u27s ability to respond profitably to environmental fluctuations by shifting factors of production within a multinational network of subsidiaries. The geographic breadth and depth of a firm\u27s multinational network are used as indicators of operational flexibility. We find there is a significantly greater coefficient between stock returns and accounting earnings for multinational firms that operate in many countries, but limit their concentration in any one foreign country, than for other multinational firms or domestic firms. This coefficient is significantly smaller for multinational firms whose foreign subsidiaries are highly concentrated in a few countries. When all multinational firms are pooled together, we find their earnings-returns association does not differ from that of domestic firms

Time to Bloom

Bloom Syndrome (BS) is an autosomal recessive disorder due to mutation in Bloom helicase (referred in literature either as BLM helicase or BLM). Patients with BS are predisposed to almost all forms of cancer. BS patients are even today diagnosed in the clinics by hyper-recombination phenotype that is manifested by high rates of Sister Chromatid Exchange. The function of BLM as a helicase and its role during the regulation of homologous recombination (HR) is well characterized. However in the last few years the role of BLM as a DNA damage sensor has been revealed. For example, it has been demonstrated that BLM can stimulate the ATPase and chromatin remodeling activities of RAD54 in vitro. This indicates that BLM may increase the accessibility of the sensor proteins that recognize the lesion. Over the years evidence has accumulated that BLM is one of the earliest proteins that accumulates at the site of the lesion. Finally BLM also acts like a "molecular node" by integrating the upstream signals and acting as a bridge between the transducer and effector proteins (which again includes BLM itself), which in turn repair the DNA damage. Hence BLM seems to be a protein involved in multiple functions - all of which may together contribute to its reported role as a "caretaker tumor suppressor". In this review the recent literature documenting the upstream BLM functions has been elucidated and future directions indicated

Financial Markets and Marketing The Tradeoff between R&D and Advertising During an Economic Downturn

This article examines the association between stock returns and earnings changes of firms that have made different tradeoffs with respect to R&D and advertising spending during an economic downturn. During the 2000–2002 bear market that was associated with a downturn in the U.S. economy, we find the coefficient that relates stock returns and earnings changes to be significantly greater for firms that increased their advertising expenditures and decreased their R&D expenditures than for firms that increased their R&D expenditures and decreased their advertising expenditures. Our results suggest that investors perceive that an increased emphasis on advertising can enable firms to stem earnings erosion that can potentially occur during an economic downturn

Student’s perception and experience of computer assisted learning as a teaching method in experimental pharmacology

Background: The decline in the use of animals for teaching in experimental pharmacology due to ethical concerns has led to the introduction of non-animal alternatives. These methods not only try to simulate the live experiment results but also offer the advantages of being time saving, reproducible and have minimum errors. One such alternative is computer assisted learning (CAL) which demonstrates the effect of drugs on living tissue in a virtual environment. In the present study, we assessed the outcome of CAL session among the medical students with the help of a questionnaire and compared it with the pre-CAL questionnaire to study the effectiveness of simulation experiments.Methods: A total of 109 students participated in the study. They were divided into two Batches I and II. Batch I students were given a pre-CAL questionnaire on a selected topic, followed by a CAL session on that topic and a post-CAL questionnaire. Whereas for Batch II students, we directly started with demonstration of CAL session on the same topic followed by a post-CAL questionnaire. A student feedback form based on five point Likert scale was also given to all the students to get their views about the simulation experiments.Results: The students in Batch I, after the CAL session had better average score % as compared to pre-CAL test (80.7% vs. 32.4%). Furthermore, when we compared the post-CAL scores of Batch I and Batch II, it was seen that the average score % was higher for Batch I (80.7%) than Batch II (55.4%).Conclusion: The study demonstrates the effectiveness of CAL in teaching experimental pharmacology concepts and the students felt that this method helped them in a better understanding of the topic as the effects were clearly visualized on the screen and that such simulations need to be a part of the standard curriculum

Characterization of cis-acting sequences involved in packaging porcine adenovirus type 311Published as VIDO Journal article no. 340.

AbstractEncapsidation of adenovirus DNA involves specific interactions between cis-acting genomic DNA sequences and trans-acting proteins. The cis-acting packaging domain located near the left inverted terminal repeat is composed of a series of redundant but not functionally equivalent motifs. Such motifs are made up of the consensus sequence 5′-TTTGN8CG-3′ and 5′-TTTG/A-3′ in human adenovirus 5 (HAV-5) and canine adenovirus-2 (CAV-2), respectively. To gain comparative insight into adenovirus encapsidation, we examined the packaging domain of porcine adenovirus-3 (PAV-3). Using deletion mutants, we localized the PAV-3 packaging domain to 319 bp (nt 212 to 531), which contains six cis-acting elements. However, this domain does not contain the consensus motifs identified in HAV-5. In addition, consensus motif found in CAV-2 is present only once in PAV-3. Instead, PAV-3 packaging domain appears to contain AT/GC-rich sequences. The packaging motifs of PAV-3, which are functionally redundant but not equivalent, are located at the left end of the genome

Further evidence for early lunar magnetism from troctolite 76535

The earliest history of the lunar dynamo is largely unknown and has important implications for the thermal state of the Moon and the physics of dynamo generation. The lunar sample with the oldest known paleomagnetic record is the 4.25 billion year old (Ga) troctolite 76535. Previous studies of unoriented subsamples of 76535 found evidence for a dynamo field with a paleointensity of several tens of microteslas. However, the lack of mutual subsample orientation prevented a demonstration that the magnetization was unidirectional, a key property of thermoremanent magnetization. Here we report further alternating field demagnetization on three mutually oriented subsamples of 76535, as well as new pressure remanent magnetization experiments to help rule out shock magnetization. We also describe new 40Ar/39Ar thermochronometry and cosmogenic neon measurements that better constrain the rock's thermal history. Although the rock is unbrecciated, unshocked, and slowly cooled, its demagnetization behavior is not ideal due to spurious remanence acquisition. Despite this limitation, all three subsamples record a high coercivity magnetization oriented in nearly the same direction, implying that they were magnetized by a unidirectional field on the Moon. We find no evidence for shock remanence, and our thermochronometry calculations show no significant reheating events since 4249 ± 12 million years ago (Ma). We infer a field paleointensity of approximately 20–40 μT, supporting the previous conclusion that a lunar dynamo existed at 4.25 Ga. The timing of this field supports an early dynamo powered by thermal or thermochemical core convection and/or a mechanical dynamo but marginally excludes a dynamo delayed by thermal blanketing from radiogenic element-rich magma ocean cumulates