Fluid sources and overpressures within the central Cascadia Subduction Zone revealed by a warm, high-flux seafloor seep.

Pythia's Oasis is a newly discovered seafloor seep on the Central Oregon segment of the Cascadia Subduction Zone, where focused venting emits highly altered fluids ~9°C above the background temperature. The seep fluid chemistry is unique for Cascadia and includes extreme enrichment of boron and lithium and depletion of chloride, potassium, and magnesium. We conclude that the fluids are sourced from pore water compaction and mineral dehydration reactions with minimum source temperatures of 150° to 250°C, placing the source at or near the plate boundary offshore Central Oregon. Estimated fluid flow rates of 10 to 30 cm s-1 are orders of magnitude higher than those estimated elsewhere along the margin and are likely driven by extreme overpressures along the plate boundary. Probable draining of the overpressured reservoir along the vertical Alvin Canyon Fault indicates the important role that such faults may play in the regulation of pore fluid pressure throughout the forearc in Central Cascadia.

Thermal biology of domestic animals.

The thermal environment is the most important ecological factor determining the growth, development, and productivity of domestic animals. Routes of energy exchange (sensible heat and latent heat) between animals and their environment are greatly influenced by body weight, fat deposition, hair-coat properties, functional activity, and number of sweat glands, as well as the presence or absence of anatomical respiratory countercurrent heat exchange capability. Differences in these anatomical features across species have led to specialization of heat exchange. Thermal plasticity and degree of acclimation are critical factors determining the ability of animals to respond to environmental change. Increases in productive capability of domestic animals can compromise thermal acclimation and plasticity, requiring greater investments in housing systems that reduce variability of the thermal environment. The combination of steadily increasing metabolic heat production as domestic animal productivity increases and a rising world temperature poses ongoing and future challenges to maintaining health and well-being of domestic animals.

Serotonin: a local regulator in the mammary gland epithelium.

Serotonin (5-hydroxytryptamine, 5-HT) is a very simple molecule that plays key roles in complex communication mechanisms within the animal body. In the mammary glands, serotonin biosynthesis and secretion are induced in response to dilation of the alveolar spaces. Since its discovery several years ago, mammary 5-HT has been demonstrated to perform two homeostatic functions. First, serotonin regulates lactation and initiates the transition into the earliest phases of involution. Second, serotonin is a local signal that induces parathyroid hormone-related peptide (PTHrP), which allows the mammary gland to drive the mobilization of calcium from the skeleton. These processes use different receptor types, 5-HT7 and 5-HT2, respectively. In this review, we provide synthetic perspectives on the fundamental processes of lactation homeostasis and the adaptation of calcium homeostasis for lactation. We analyze the role of the intrinsic serotonin system in the physiological regulation of the mammary glands. We also consider the importance of the mammary serotonin system in pathologies and therapies associated with lactation and breast cancer.

Meta-analysis of the effects of sometribove zinc suspension on the production and health of lactating dairy cows.

OBJECTIVE: To provide an updated evaluation of the efficacy and safety of sometribove zinc suspension (rbST-Zn), a form of recombinant bovine somatotropin, in lactating dairy cows. DESIGN: Meta-analysis. SAMPLE: 26 studies published in peer-reviewed journals or reviewed by a regulatory agency. PROCEDURES: To be included, a study had to involve the use of the rbST-Zn formulation available to US producers in accordance with the label instructions for treatment initiation (57 to 70 days postpartum), dose (500 mg, q 14 d), and route (SC). RESULTS: For cows treated with rbST-Zn, mean milk, 3.5% fat-corrected milk, fat, and protein yields were increased by 4.00, 4.04, 0.144, and 0.137 kg/d (8.8, 8.89, 0.32, and 0.30 lb/d), respectively; however, the concentration of milk components did not change. Pregnancy proportion for the first 2 breeding cycles was increased by 5.4%, and pregnancy proportion for the duration of the trial was reduced by 5.5% for rbST-Zn-treated cows, compared with proportions for untreated cows. Mean body condition score (1 to 5 scale) was reduced by 0.06 points during the period of rbST-Zn use for treated cows. Administration of rbST-Zn had no effect on milk somatic cell count, the number of days to pregnancy, or inseminations per pregnancy; rates of fetal loss, twins, cystic ovaries, clinical lameness, lameness lesions, or traumatic lesions of the integumentary system; and odds of clinical mastitis or culling. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that rbST-Zn administration to dairy cows effectively increases milk production with no adverse effects on cow health and well-being.

CEP biomarkers as potential tools for monitoring therapeutics.

BACKGROUND: Carboxyethylpyrrole (CEP) adducts are oxidative modifications derived from docosahexaenoate-containing lipids that are elevated in ocular tissues and plasma in age-related macular degeneration (AMD) and in rodents exposed to intense light. The goal of this study was to determine whether light-induced CEP adducts and autoantibodies are modulated by pretreatment with AL-8309A under conditions that prevent photo-oxidative damage of rat retina. AL-8309A is a serotonin 5-HT1A receptor agonist. METHODS: Albino rats were dark adapted prior to blue light exposure. Control rats were maintained in normal cyclic light. Rats were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0 hours) before light exposure for 6 h (3.1 mW/cm(2), λ=450 nm). Animals were sacrificed immediately following light exposure and eyes, retinas and plasma were collected. CEP adducts and autoantibodies were quantified by Western analysis or ELISA. RESULTS: ANOVA supported significant differences in mean amounts of CEP adducts and autoantibodies among the light + vehicle, light + drug and dark control groups from both retina and plasma. Light-induced CEP adducts in retina were reduced ~20% following pretreatment with AL-8309A (n = 62 rats, p = 0.006) and retinal CEP immunoreactivity was less intense by immunohistochemistry. Plasma levels of light-induced CEP adducts were reduced at least 30% (n = 15 rats, p = 0.004) by drug pretreatment. Following drug treatment, average CEP autoantibody titer in light exposed rats (n = 22) was unchanged from dark control levels, and ~20% (p = 0.046) lower than in vehicle-treated rats. CONCLUSIONS: Light-induced CEP adducts in rat retina and plasma were significantly decreased by pretreatment with AL-8309A. These results are consistent with and extend previous studies showing AL-8309A reduces light-induced retinal lesions in rats and support CEP biomarkers as possible tools for monitoring the efficacy of select therapeutics.

Report on residency training information (2011-2012), American Board of Emergency Medicine.

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine residency training programs and the residents in those programs. We present the 2012 annual report on the status of US emergency medicine training programs.

Report of the Task Force on Residency Training Information (2010-2011), American Board of Emergency Medicine.

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine residency training programs and the residents in those programs. We present the 2011 annual report on the status of US emergency medicine training programs.

Complement deposition and microglial activation in the outer retina in light-induced retinopathy: inhibition by a 5-HT1A agonist.

PURPOSE: Increasing evidence supports a role for complement in the pathogenesis of age-related macular degeneration (AMD). This study evaluated retinal microglia, T-lymphocytes, and complement deposition in a light-induced retinopathy model. The effect of a serotonin (5-hydroxytryptamine, 5-HT(1A)) agonist on these processes was investigated. METHODS: Rats were dark adapted for 24 hours before a 6-hour blue light exposure. Some animals were predosed subcutaneously with AL-8309A. Retinas were evaluated at different times after light exposure. Paraffin sections were stained with antibody for a microglial marker (Iba1), a T-lymphocyte marker (CD3), and complement components C1q, C3, factor B, factor H, and membrane attack complex (MAC). RESULTS: Light exposure resulted in substantial photoreceptor and RPE loss. Robust microglia activation and migration to the outer retina occurred rapidly. Substantial T-lymphocyte recruitment did not occur. Complement alternative pathway was strongly activated, resulting in the deposition of C3, factor B, factor H, and MAC in the area of photic lesions. Dosing with AL-8309A prevented retinal lesions and decreased microglia activation/recruitment and complement deposition in the outer retina. CONCLUSIONS: In blue light exposed retinas, microglia were activated and migrated toward the outer retina, whereas a T-lymphocyte response was minimal. The innate immune system was markedly activated, with substantial complement deposition in the outer retina after light exposure. This complement deposition was prevented by AL-8309A. This model may be useful in the evaluation of complement inhibitors and other neuroprotectants intended for ocular use. AL-8309 is under evaluation in the clinic and may be useful in the treatment of AMD.

Agonists at the serotonin receptor (5-HT(1A)) protect the retina from severe photo-oxidative stress.

PURPOSE: 5-HT(1A) agonists are neuroprotective in CNS injury models. The authors evaluated the efficacy of 5-HT(1A) agonists to protect the retina from severe blue light-induced photo-oxidative damage. METHODS: Albino rats were dosed (subcutaneously) with AL-8309A, 8-OH DPAT, or buspirone once or three times before 6-hour exposure to blue light. Electroretinograms (ERGs) were measured to assess retinal function, and retinal damage was evaluated by light microscopy. Topical ocular dosing with 1.75% AL-8309B was also evaluated. Rats were dosed with WAY-100635, a 5-HT(1A) antagonist, to determine whether protection required activation of the 5-HT(1A) receptor. RESULTS: ERG response amplitudes were significantly (P < 0.05) depressed more than 66% in vehicle-dosed rats after light exposure. ERGs were significantly higher in rats treated with AL-8309A (0.1-30 mg/kg), 8-OH DPAT (0.1-1 mg/kg), buspirone (5-20 mg/kg) or topical ocular with 1.75% AL-8309B. Retinas from AL-8309A and 8-OH DPAT-treated rats were devoid of histologic lesions. Significant protection was measured in rats dosed once 0, 24, or 48 hours before light exposure. Protection provided by dosing with AL-8309B or 8-OH DPAT was inhibited in rats predosed with WAY-100635. CONCLUSIONS: 5-HT(1A) agonists provided potent and complete functional and structural protection. Protection was inhibited by treatment with WAY-100635, confirming the requirement for activating the 5-HT(1A) receptor in initiating this survival pathway. Single-dose experiments with AL-8309A suggest that the mechanism of protection is rapidly activated and protection persists for 48 hours. AL-8309B (1.75%) was effective after topical ocular dosing. AL-8309B is under evaluation in the clinic and may be useful in treating age-related macular degeneration.

Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle.

The regulation of mitochondrial biogenesis and function in the lactating mammary cell is poorly understood. The goal of this study was to use proteomics to relate temporal changes in mammary cell mitochondrial function during lactation to changes in the proteins that make up this organelle. The hypothesis tested was that changes in mammary cell mitochondrial biogenesis and function during lactation would be accounted for by coordinated changes in the proteins of the electron transport chain and that some of these proteins might be linked by their expression patterns to PPARGC1α and AMP kinase. The mitochondrial proteome was studied along with markers of mitochondrial biogenesis and function in mammary tissue collected from mice over the course of a single prolonged lactation cycle. Mammary tissue concentrations of AMP and ADP were increased (P < 0.05) during early lactation and then declined with prolonged lactation. Similar changes were also observed for mitochondrial ATP synthesis activity, mitochondrial mass and DNA copy number. Analysis of the mammary cell mitochondrial proteome identified 244 unique proteins. Of these, only two proteins of the electron transport chain were found to increase during early lactation. In contrast, coordinated changes in numerous electron transport chain proteins were observed both during mid- and late lactation. There were six proteins that could be directly linked to PPARGC1α through network analysis. Abundance of PPARGC-1α and phosphorylation of AMP kinase was highest on day 2 postpartum. The results suggest that the increases in mammary mitochondria ATP synthesis activity during early lactation results from changes in only a limited number proteins. In addition, decreases in a handful of proteins linked to lipid oxidation could be temporally linked to decreases in PPARGC1α and phospho-AMP kinase suggesting potential roles for these proteins in coordinating mammary gland metabolism during early lactation.

Report of the Task Force on Residency Training Information (2009-2010), American Board of Emergency Medicine.

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine residency training programs and the residents in those programs. We present the 2010 annual report on the status of US emergency medicine training programs.

The bovine mammary gland expresses multiple functional isoforms of serotonin receptors.

Recent studies in dairy cows have demonstrated that serotonergic ligands affect milk yield and composition. Correspondingly, serotonin (5-HT) has been demonstrated to be an important local regulator of lactational homeostasis and involution in mouse and human mammary cells. We determined the mRNA expression of bovine 5-HT receptor (HTR) subtypes in bovine mammary tissue (BMT) and used pharmacological agents to evaluate functional activities of 5-HT receptors. The mRNAs for five receptor isoforms (HTR1B, 2A, 2B, 4, and 7) were identified by conventional real-time (RT)-PCR, RT quantitative PCR, and in situ hybridization in BMT. In addition to luminal mammary epithelial cell expression, HTR4 was expressed in myoepithelium, and HTR1B, 2A, and 2B were expressed in small mammary blood vessels. Serotonin suppressed milk protein mRNA expression (alpha-lactalbumin and beta-casein mRNA) in lactogen-treated primary bovine mammary epithelial cell (BMEC) cultures. To probe the functional activities of individual receptors, caspase-3 activity and expression of alpha-lactalbumin and beta-casein were measured. Both SB22489 (1B antagonist) and ritanserin (2A antagonist) increased caspase-3 activity. Expression of alpha-lactalbumin and beta-casein mRNA levels in BMEC were stimulated by low concentrations of SB224289, ritanserin, or pimozide. These results demonstrate that there are multiple 5-HT receptor isoforms in the bovine mammary gland, and point to profound differences between serotonergic systems of the bovine mammary gland and the human and mouse mammary glands. Whereas human and mouse mammary epithelial cells express predominately the protein for the 5-HT(7) receptor, cow mammary epithelium expresses multiple receptors that have overlapping, but not identical, functional activities.

Report of the Task Force on Residency Training Information (2008-2009), American Board of Emergency Medicine.

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine residency training programs and the residents in those programs. We present the 2009 annual report on the status of US emergency medicine residency programs.

Report of the Task Force on Residency Training Information (2007-2008), American Board of Emergency Medicine.

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine residency training programs and the residents training in those programs. We present the eleventh annual report on the status of US emergency medicine residency programs.

Effects of recombinant bovine somatotropin (rbST) and season on plasma and milk insulin-like growth factors I (IGF-I) and II (IGF-II) in lactating dairy cows.

During two studies, effects of recombinant bovine somatotropin (rbST) on plasma and milk IGF's in cows adapted to summer (S; 12 cows) or winter (W; 12 cows) conditions were evaluated. Each study consisted of on-farm periods (30 days) followed by climatology chamber periods (CC; 30 days). Cows were given daily injections of rbST, Sometribove, USAN (25mg/day; 6 cows each study) or saline (control; 6 cows each study). During on-farm periods, blood and milk (am and pm) samples were collected once weekly. During CC periods, blood samples were collected every 2 days and milk samples (am and pm) were collected daily. Plasma IGF-I and IGF-II were increased in cows treated with rbST. A pronounced seasonal pattern in basal and rbST-stimulated plasma IGF-I but not IGF-II was detected. Higher basal and rbST-stimulated plasma IGF-I concentrations in S occurred despite large decreases in feed intake and energy balance. Milk IGF-I and IGF-II was not affected by rbST treatment or season. Although milk IGF-I and IGF-II concentrations were unaffected by rbST treatment, total IGF-output increased due to increased milk yield. The observed seasonal patterns in plasma IGF-I may be indicative of seasonal differences in the coupling of the somatotropin-IGF axis. In particular, we failed to detect an uncoupling of the somatotropin-IGF-I axis in S despite an induced negative energy balance during thermal stress.

Photic injury promotes cleavage of p75NTR by TACE and nuclear trafficking of the p75 intracellular domain.

The p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis factor receptor superfamily that paradoxically mediates neuronal survival and differentiation or apoptotic cell death. Cleavage of p75NTR by a constitutively active metalloprotease could result in shedding of its extracellular domain (p75ECD) and generation of a pro-apoptotic intracellular domain (p75ICD). In this study, we established that exposure of a transgenic mouse photoreceptor cell line to intense light upregulated the expression of p75NTR and of the disintegrin metalloprotease tumor necrosis factor-converting enzyme (TACE) and resulted in apoptotic cell death. Light damage promoted TACE cleavage of p75NTR resulting in shedding of the soluble p75ECD and nuclear translocation of the p75ICD. Overexpression of TACE and p75NTR-induced p75NTR cleavage and secretion of p75ECD, but not nuclear transport of p75ICD. Light-induced cleavage of p75NTR, nuclear localization of p75ICD, and apoptosis were inhibited by IC-3, a metalloprotease inhibitor. Increased levels of p75NTR and TACE were observed in photoreceptor cells of animals with photic injury. Our findings support a role for TACE in the proteolytic cleavage of p75NTR and light-induced apoptosis.

Report of the Task Force on Residency Training Information (2006-2007), American Board of Emergency Medicine.

The American Board of Emergency Medicine (ABEM) gathers extensive background information on emergency medicine residency training programs and the residents training in those programs. We present the tenth annual report on the status of US emergency medicine residency programs.

Hybrid feedforward-feedback active noise reduction for hearing protection and communication.

A hybrid active noise reduction (ANR) architecture is presented and validated for a circumaural earcup and a communication earplug. The hybrid system combines source-independent feedback ANR with a Lyapunov-tuned leaky LMS filter (LyLMS) improving gain stability margins over feedforward ANR alone. In flat plate testing, the earcup demonstrates an overall C-weighted total noise reduction of 40 dB and 30-32 dB, respectively, for 50-800 Hz sum-of-tones noise and for aircraft or helicopter cockpit noise, improving low frequency (<100 Hz) performance by up to 15 dB over either control component acting individually. For the earplug, a filtered-X implementation of the LyLMS accommodates its nonconstant cancellation path gain. A fast time-domain identification method provides a high-fidelity, computationally efficient, infinite impulse response cancellation path model, which is used for both the filtered-X implementation and communication feedthrough. Insertion loss measurements made with a manikin show overall C-weighted total noise reduction provided by the ANR earplug of 46-48 dB for sum-of-tones 80-2000 Hz and 40-41 dB from 63 to 3000 Hz for UH-60 helicopter noise, with negligible degradation in attenuation during speech communication. For both hearing protectors, a stability metric improves by a factor of 2 to several orders of magnitude through hybrid ANR.