Chemotherapy for prostate cancer: implementing early systemic therapy to improve outcomes

Prostate cancer remains a significant health concern for men in the USA as it is a leading cancer diagnosis and a cause of death. With the use of prostate-specific antigen or screening, a stage migration has occurred with an increase in the number of men diagnosed with early-stage disease. The optimal primary management of these men is evolving, but despite adequate local treatment a significant percentage will develop either biochemical or clinical evidence of recurrent disease. Several criteria for risk stratification have been developed, thus, improving the ability to identify a high-risk population. Small studies have been reported demonstrating the feasibility of neoadjuvant or adjuvant chemotherapy in conjunction with either radiation or radical prostatectomy in this high-risk population, and large phase III studies are ongoing. With the advent of life-prolonging chemotherapy in the hormone-refractory setting, attention must now also be given to early-stage disease so as to develop multi-modality approaches with the hope of increasing survival and ultimately providing a cure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46931/1/280_2005_Article_103.pd

Systematic map of reproductive performance of female cattle in Africa

This protocol uses the Systematic Review Protocol for Animal Intervention Studies by Syrcle (www.syrcle.nl)This is a protocol for undertaking a systematic review of reproductive performance of female cattle in Africa. The objective of the review is to prepare a systematic evidence map of ruminant reproduction. The map will help to define the current state of ruminant reproduction in different production systems and ecosystems, and will identify current trends, barriers to improvements, and potential solutions

Morphodynamics of a width-variable gravel bed stream: new insights on pool-riffle formation from physical experiments

Field observations, experiments, and numerical simulations suggest that pool-riffles along gravel bed mountain streams develop due to downstream variations of channel width. Where channels narrow, pools are observed, and at locations of widening, riffles occur. Based on previous work, we hypothesize that the bed profile is coupled to downstream width variations through momentum fluxes imparted to the channel surface, which scale with downstream changes of flow velocity. We address this hypothesis with flume experiments understood through scaling theory. Our experiments produce pool-riffle like structures across average Shields stresses t* that are a factor 1.5–2 above the threshold mobility condition of the experimental grain size distribution. Local topographic responses are coupled to channel width changes, which drive flows to accelerate or decelerate on average, for narrowing and widening, respectively. We develop theory which explains the topography-width-velocity coupling as a ratio of two reinforcing timescales. The first timescale captures the time necessary to do work to the channel bed. The second timescale characterizes the relative time magnitude of momentum transfer from the flowing fluid to the channel bed surface. Riffle-like structures develop where the work and momentum timescales are relatively large, and pools form where the two timescales are relatively small. We show that this result helps to explain local channel bed slopes along pool-riffles for five data sets representing experimental, numerical, and natural cases, which span 2 orders of magnitude of reach-averaged slope. Additional model testing is warranted.Peer ReviewedPostprint (published version

A critical role for astrocytes in hypercapnic vasodilation in brain

Cerebral blood flow (CBF) is controlled by arterial blood pressure, arterial CO2, arterial O2, and brain activity and is largely constant in the awake state. Although small changes in arterial CO2 are particularly potent to change CBF (1 mmHg variation in arterial CO2 changes CBF by 3-4%), the coupling mechanism is incompletely understood. We tested the hypothesis that astrocytic prostaglandin E2 (PgE2) plays a key role for cerebrovascular CO2 reactivity and that preserved synthesis of glutathione is essential for the full development of this response. We combined two-photon imaging microscopy in brain slices with in vivo work in rats and C57Bl/6J mice to examine the hemodynamic responses to CO2 and somatosensory stimulation before and after inhibition of astrocytic glutathione and PgE2 synthesis. We demonstrate that hypercapnia (increased CO2) evokes an increase in astrocyte [Ca2+]i and stimulates COX-1 activity. The enzyme downstream of COX-1 that synthesizes PgE2 (microsomal prostaglandin E synthase-1) depends critically for its vasodilator activity on the level of glutathione in the brain. We show that when glutathione levels are reduced, astrocyte calcium-evoked release of PgE2 is decreased and vasodilation triggered by astrocyte [Ca2+]i in vitro and by hypercapnia in vivo is inhibited. Astrocyte synthetic pathways, dependent on glutathione, are involved in cerebrovascular reactivity to CO2. Reductions in glutathione levels in ageing, stroke or schizophrenia could lead to dysfunctional regulation of CBF and subsequent neuronal damage

Primary bony non-Hodgkin lymphoma of the cervical spine: a case report

<p>Abstract</p> <p>Introduction</p> <p>Non-Hodgkin lymphoma primarily originating from the bone is exceedingly rare. To our knowledge, this is the first report of primary bone lymphoma presenting with progressive cord compression from an origin in the cervical spine. Herein, we discuss the unusual location in this case, the presenting symptoms, and the management of this disease.</p> <p>Case presentation</p> <p>We report on a 23-year-old Caucasian-American man who presented with two months of night sweats, fatigue, parasthesias, and progressive weakness that had progressed to near quadriplegia. Magnetic resonance (MR) imaging demonstrated significant cord compression seen primarily at C7. Surgical management, with corpectomy and dorsal segmental fusion, in combination with adjuvant chemotherapy and radiation therapy, halted the progression of the primary disease and preserved neurological function. Histological analysis demonstrated an aggressive anaplastic large cell lymphoma.</p> <p>Conclusion</p> <p>Isolated primary bony lymphoma of the spine is exceedingly rare. As in our case, the initial symptoms may be the result of progressive cervical cord compression. Anterior corpectomy with posterolateral decompression and fusion succeeded in preventing progressive neurologic decline and maintaining quality of life. The reader should be aware of the unique presentation of this disease and that surgical management is a successful treatment strategy.</p

Evaluation of Formulas for Predicting Various Components of Mixed Herd Milk

The Oklahoma Agricultural Experiment Station periodically issues revisions to its publications. The most current edition is made available. For access to an earlier edition, if available for this title, please contact the Oklahoma State University Library Archives by email at [email protected] or by phone at 405-744-6311

Turbulence, instream wood and fish: ecohydraulic interactions under field conditions

This is the pre-peer reviewed version of the following article: Trinci, G, Harvey, GL, Henshaw, AJ, Bertoldi, W, Hölker, F. Turbulence, instream wood and fish: Ecohydraulic interactions under field conditions. Ecohydrology. 2020;e2211. https://doi.org/10.1002/eco.2211 , which has been published in final form at https://doi.org/10.1002/eco.2211. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Births in two different delivery units in the same clinic – A prospective study of healthy primiparous women

Background: Earlier studies indicate that midwife-led birth settings are associated with modest benefits, including reduced medical interventions and increased maternal satisfaction. The generalizability of these studies to birth settings with low intervention rates, like those generally found in Norway, is not obvious. The aim of the present study was to compare intervention rates associated with labour in low-risk women who begin their labour in a midwife-led unit and a conventional care unit. Methods: Eligible participants were low-risk primiparas who met the criteria for delivery in the midwife-led ward regardless of which cohort they were allocated to. The two wards are localised at the same floor. Women in both cohorts received the same standardized public antenatal care by general medical practitioners and midwifes who were not involved in the delivery. After admission of a woman to the midwife-led ward, the next woman who met the inclusion criteria, but preferred delivery at the conventional delivery ward, was allocated to the conventional delivery ward cohort. Among the 252 women in the midwife-led ward cohort, 74 (29%) women were transferred to the conventional delivery ward during labour. Results: Emergency caesarean and instrumental delivery rates in women who were admitted to the midwife-led and conventional birth wards were statistically non-different, but more women admitted to the conventional birth ward had episiotomy. More women in the conventional delivery ward received epidural analgesia, pudental nerve block and nitrous oxide, while more women in the midwife-led ward received opiates and non-pharmacological pain relief. Conclusion: We did not find evidence that starting delivery in the midwife-led setting offers the advantage of lower operative delivery rates. However, epidural analgesia, pudental nerve block and episiotomies were less often while non-pharmacological pain relief was often used in the midwifeled ward

Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging