Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs).

Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed

Antibody responses to a Cryptosporidium parvum rCP15/60 vaccine

Cryptosporidium parvum is a zoonotic apicomplexa-protozoan pathogen that causes gastroenteritis and diarrhoea in mammals worldwide. The organism is transmitted by ingestion of oocysts, which are shed in faeces, and completes its lifecycle in a single host.^1^ C. parvum is ubiquitous on dairy operations worldwide and is one of the leading causes of diarrhoea in calves on these farms.^2,3^ Here, for the first time, we describe the antibody response in a large group of cows to a recombinant C. parvum oocyst surface protein (rCP15/60) vaccine and the antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. Results of recent genotype surveys indicate that calves are the only major reservoir for C. parvum infections in humans.^4^ Human C. parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDs patients.^4^ Drug therapy against cryptosporidiosis is limited and not wholly efficacious in either humans or calves^5^, making development of an effective vaccine of paramount importance. To date, there is no commercially available effective vaccine against C. parvum, although passive immunization utilizing different zoite surface (glyco)proteins has showed promise.^6-9^ All cows we vaccinated produced an antibody response to the rCP15/60 vaccine and the magnitude of response correlated strongly with the subsequent level of antibody in their colostrum. All calves fed rCP15/60-immune colostrum showed a dose-dependent absorption of antibody. Our results demonstrate that vaccination of cows with rCP15/60 successfully induces antibodies against CP15/60 in their serum and colostrum and that these antibodies are then well absorbed when fed to neonatal calves. With further research, this C. parvum vaccine may well be a practical method of conferring passive protection to calves against cryptosporidiosis. Furthermore, a specifically targeted immune-colostrum may be valuable in protection and treatment of immunocompromised human patients with cryptosporidiosis

Effects of Farrowing Stall Layout and Number of Heat Lamps on Sow and Piglet Production Performance

Most farrowing facilities in the United States use stalls and heat lamps to improve sow and piglet productivity. This study investigated these factors by comparing production outcomes for three different farrowing stall layouts (traditional, expanded creep area, expanded sow area) and use of one or two heat lamps. Data were collected on 427 sows and their litters over one year. Results showed no statistical differences due to experimental treatment for any of the production metrics recorded, excluding percent stillborn. Parity one sows had fewer piglets born alive (p \u3c 0.001), lower percent mortality (p = 0.001) and over-lay (p = 0.003), and a greater number of piglets weaned (p \u3c 0.001) with lower average daily weight gain (ADG) (p \u3c 0.001) and more uniform litters (p = 0.001) as compared to higher parity sows. Farrowing turn, associated with group/seasonal changes, had a significant impact on most of the production metrics measured. Number of piglets born influenced the percent stillborn (p \u3c 0.001). Adjusted litter size had a significant impact on percent mortality (p \u3c 0.001), percent over-lay (p \u3c 0.001), and number of piglets weaned (p \u3c 0.001). As the number of piglets weaned per litter increased, both piglet ADG and litter uniformity decreased (p \u3c 0.001). This information can be used to guide producers in farrowing facility design

Effects of Farrowing Stall Layout and Number of Heat Lamps on Sow and Piglet Production Performance

Most farrowing facilities in the United States use stalls and heat lamps to improve sow and piglet productivity. This study investigated these factors by comparing production outcomes for three different farrowing stall layouts (traditional, expanded creep area, expanded sow area) and use of one or two heat lamps. Data were collected on 427 sows and their litters over one year. Results showed no statistical differences due to experimental treatment for any of the production metrics recorded, excluding percent stillborn. Parity one sows had fewer piglets born alive (p \u3c 0.001), lower percent mortality (p = 0.001) and over-lay (p = 0.003), and a greater number of piglets weaned (p \u3c 0.001) with lower average daily weight gain (ADG) (p \u3c 0.001) and more uniform litters (p = 0.001) as compared to higher parity sows. Farrowing turn, associated with group/seasonal changes, had a significant impact on most of the production metrics measured. Number of piglets born influenced the percent stillborn (p \u3c 0.001). Adjusted litter size had a significant impact on percent mortality (p \u3c 0.001), percent over-lay (p \u3c 0.001), and number of piglets weaned (p \u3c 0.001). As the number of piglets weaned per litter increased, both piglet ADG and litter uniformity decreased (p \u3c 0.001). This information can be used to guide producers in farrowing facility design

Study protocol for a randomised controlled trial of invasive versus conservative management of primary spontaneous pneumothorax

INTRODUCTION: Current management of primary spontaneous pneumothorax (PSP) is variable, with little evidence from randomised controlled trials to guide treatment. Guidelines emphasise intervention in many patients, which involves chest drain insertion, hospital admission and occasionally surgery. However, there is evidence that conservative management may be effective and safe, and it may also reduce the risk of recurrence. Significant questions remain regarding the optimal initial approach to the management of PSP

Motor neuron loss in aging and amyotrophic lateral sclerosis: different fuse lengths, same explosion

Advanced age and amyotrophic lateral sclerosis (ALS) are both associated with a loss of motor neurons resulting in muscle fiber atrophy and muscle weakness. Aging associated muscle fiber atrophy and weakening is termed sarcopenia, but the association with motor neuron loss is not as clearly established as in ALS, probably related to the prolonged time course of aging-related changes. Although aging and ALS effects on limb muscle strength and neuromotor performance are serious, such effects on the diaphragm muscle can be life threatening. Converging evidence indicates that larger phrenic motor neurons, innervating more fatigable type IIx and/or IIb diaphragm muscle fibers (fast fatigue intermediate, FInt and fast fatigable, FF motor units) are more susceptible to degeneration with both aging and ALS compared to smaller phrenic motor neurons innervating type I and IIa diaphragm muscle fibers (slow and fast fatigue resistant motor units, respectively). The etiology of ALS and age-related loss of motor neurons appears to involve mitochondrial function and neuroinflammation, both chronic and acute exacerbation. How mitochondrial dysfunction, neuroinflammation and motor neuron size intersect is the focus of continuing investigation.La edad avanzada y la esclerosis lateral amiotrofica (ALS) están asociadas con una pérdida de neuronas motoras que produce atrofia de las fibras musculares y debilidad muscular. El envejecimiento asociado a atrofia y debilitamiento de las fibras musculares se denomina sarcopenia, pero la asociación con la pérdida de neuronas motoras no está tan claramente establecida como en la ALS, hecho probablemente relacionado con el curso prolongado de los cambios que ocurren durante el envejecimiento. Aunque el envejecimiento y los efectos de la ALS sobre la fuerza muscular de las extremidades y el rendimiento neuromotor son graves, tales efectos sobre el músculo del diafragma pueden ser potencialmente mortales. La evidencia convergente indica que las neuronas motoras frénicas más grandes, que inervan fibras musculares de diafragma tipo IIx y/o IIb más fatigables (unidades motoras FF de fatiga rápida intermedia, FInt y fatigable rápida) son más susceptibles a la degeneración con el envejecimiento y la ALS en comparación con las neuronas motoras más pequeñas del nervio frénico que inervan las fibras musculares del diafragma tipo I y IIa (unidades motoras lentas y rápidas resistentes a la fatiga, respectivamente). La etiología de la ALS y la pérdida de neuronas motoras relacionadas con la edad parece implicar la función mitocondrial y la neuroinflamación, tanto la exacerbación crónica como la aguda. La forma en que se cruzan la disfunción mitocondrial, la neuroinflamación y el tamaño de la neurona motora es el foco de una continua investigación.Sociedad Argentina de Fisiologí

Integrative Model of Oxidative Stress Adaptation in the Fungal Pathogen Candida albicans

Acknowledgments We are grateful to the Ian Fraser Cytometry Centre and our Mass Spetrometry and qPCR Facilities for help with the flow cytometry, glutathione and qRT-PCR assays, respectively. We also thank our many colleagues in the CRISP Consortium and in the medical mycology and systems biology communities for insightful discussions. Funding: This work was supported by the CRISP project (Combinatorial Responses In Stress Pathways), which was funded by the UK Biotechnology and Biological Research Council (www.bbsrc.ac.uk): AJPB, KH, CG, ADM, NARG, MT, MCR. (Research Grants; BB/F00513X/1, BB/F005210/1-2). AJPB and JQ received additional support from the BBSRC (Research Grants; BB/K016393/1; BB/K017365/1). NARG and AJPB were also supported by the Wellcome Trust (www.wellcome.ac.uk), (Grants: 080088; 097377). AJPB was also supported by the European Research Council (http://erc.europa.eu/), (STRIFE Advanced Grant; ERC-2009-AdG-249793). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The Alor-Pantar languages: History and typology. Second edition.

The Alor-Pantar family constitutes the westernmost outlier group of Papuan (Non-Austronesian) languages. Its twenty or so languages are spoken on the islands of Alor and Pantar, located just north of Timor, in eastern Indonesia. Together with the Papuan languages of Timor, they make up the Timor-Alor-Pantar family. The languages average 5,000 speakers and areunder pressure from the local Malay variety as well as the national language, Indonesian. This volume studies the internal and external linguistic history of thisinteresting group, and showcases some of its unique typological features, such as the preference to index the transitive patient-like argument on the verb but not the agent-like one; the extreme variety in morphological alignment patterns; the use of plural number words; the existence of quinary numeral systems; the elaborate spatial deictic systems involving an elevation component; and the great variation exhibited in their kinship systems. Unlike many other Papuan languages, Alor-Pantar languages do not exhibit clause-chaining, do not have switch reference systems, never suffix subject indexes to verbs, do not mark gender, but do encode clusivity in their pronominal systems. Indeed, apart from a broadly similar head-final syntactic profile, there is little else that the Alor-Pantar languages share with Papuan languages spoken in other regions. While all of them show some traces of contact with Austronesian languages, in general, borrowing from Austronesian has not been intense, and contact with Malay and Indonesian is a relatively recent phenomenon in most of the Alor-Pantar region.   This is the second edition of the volume that was originally published in 2014, as one of the first open access publications of Language Science Press. In less than three years, the first edition had more than 10,000 downloads, many of which in Indonesia, and downloads are still increasing. To us this demonstrates how important it is to use use free open access to enable both scientists and speakers of local languages in Indonesia to read this work. In this second edition, typographical errors have been corrected, some small textual improvements have been implemented, broken URL links repaired or removed, and maps and references updated. The overall content of the chapters has not been changed