Objectives were to study effects of seasonal variation and feed additives on milk fatty acid (FA) composition of dairy cows fed fresh alfalfa based diets. To meet the first objective, a survey of ...eight selected alfalfa-grazing dairy farms was conducted in which the farms were visited four times in the four seasons of the year to obtain information on diet composition, herd management, days in milk (DIM) and milk yield. The proportion of alfalfa pasture in the total diet averaged 680
±
167
g/kg of dry matter (DM), and estimated DM intake and milk yield averaged 15.0 and 15.1
kg/cow/d, respectively. Mean concentrations of conjugated linoleic acid (CLA) (13.6
g/kg fat) and
trans 18:1 (48
g/kg fat) were positively associated with the proportion of alfalfa in the diets, while short chain FA (
i.e., C4–C14) proportions of milk FA were lower in spring high alfalfa diets
versus winter low alfalfa diets with intermediate values in summer and autumn. The opposite trend occurred for most of the medium and long-chain FA (
i.e., >C14). Seasonal variations of milk FA composition were associated with the proportion of alfalfa pasture in the diet, particularly for CLA and
trans 18:1. To study effects of feed additives on milk FA composition of milk from dairy cows fed fresh alfalfa based diets, impacts on milk FA composition of different feed additives used to control rumen fermentation was evaluated. The treatments were a control diet (Control), composed of
ad libitum freshly cut pre-bloom alfalfa pasture, and three feed additives: Control
+200
g/cow/d of dietary buffers (DB; calcium carbonate 400
g/kg; sodium bicarbonate 300
g/kg; magnesium oxide 150
g/kg; bentonite 150
g/kg), Control
+
antibiotics (MV; 300
mg
monensin/cow/d and 30
mg
virginiamycin/cow/d) and Control
+
15
g/cow/d of a yeast culture (YC). No feed additives affected DM intake, milk yield, milk composition or milk FA composition, including CLA (12.9
g/kg milk FA), in mid lactation primiparous or late lactation multiparous dairy cows fed fresh alfalfa, and there were no differences between primiparous and multiparous cows in milk FA composition.
Mycophenolate mofetil is commonly used as a steroid-sparing agent effective in the management of erythema nodosum, idiopathic nodular panniculitis (Pfiefer-Weber-Christian disease), bullous ...pemphigoid, pemphigus vulgaris, and psoriasis. We report a case of nodular vasculitis responsive to mycophenolate mofetil. The clinical presentation, etiology, and management options for nodular vasculitis are discussed.
GluR6 is a glutamate receptor of the kainate subtype that is expressed in the mammalian central nervous system. The cDNA coding for the rat brain receptor was subcloned into a baculovirus expression ...vector and the purified recombinant virus was used to infect Spodoptera frugiperda (Sf9) insect cells. The pharmacological profile and the status of several post-translational modifications of the GluR6 protein were analyzed. Saturation analyses of 3Hkainic acid binding demonstrated that GluR6 expressed in Sf9 cell membranes bound 3Hkainic acid at a single high affinity site with a dissociation constant of 12 nM. Competition studies indicated the inhibitory potencies of various excitatory amino acids, including the potent neurotoxin domoic acid, were comparable to those observed in mammalian brain tissue. Immunoblots of infected Sf9 cell membranes using an anti-GluR6 antibody revealed two immunoreactive bands. Enzymatic deglycosylation indicated that the higher molecular weight form corresponded to the glycosylated receptor whereas the lower molecular weight form corresponded to the unglycosylated protein. The phosphorylation of GluR6 by cyclic AMP-dependent and cyclic GMP-dependent protein kinase was examined in partially purified preparations of the receptor. GluR6 was phosphorylated by cyclic AMP but not by cyclic GMP-dependent protein kinase in vitro. These results indicate that GluR6 expressed in Sf9 cells has similar pharmacological properties and is processed post-translationally in a manner similar to GluR6 expressed in mammalian cells and tissues. The ease of production and the high levels of expression in baculovirus-infected insect cells relative to other expression systems should facilitate further biochemical and pharmacological characterization of this receptor.
A fundamental objective of anesthesia research is to identify the receptors and brain regions that mediate the various behavioral components of the anesthetic state, including amnesia, immobility, ...and unconsciousness. Using complementary
in vivo
and
in vitro
approaches, we found that GABA
A
receptors that contain the α5 subunit (α5GABA
A
Rs) play a critical role in amnesia caused by the prototypic intravenous anesthetic etomidate. Whole-cell recordings from hippocampal pyramidal neurons showed that etomidate markedly increased a tonic inhibitory conductance generated by α5GABA
A
Rs, whereas synaptic transmission was only slightly enhanced. Long-term potentiation (LTP) of field EPSPs recorded in CA1 stratum radiatum was reduced by etomidate in wild-type (WT) but not α5 null mutant (α5−/−) mice. In addition, etomidate impaired memory performance of WT but not α5−/− mice for spatial and nonspatial hippocampal-dependent learning tasks. The brain concentration of etomidate associated with memory impairment
in vivo
was comparable with that which increased the tonic inhibitory conductance and blocked LTP
in vitro
. The α5−/− mice did not exhibit a generalized resistance to etomidate, in that the sedative-hypnotic effects measured with the rotarod, loss of righting reflex, and spontaneous motor activity were similar in WT and α5−/− mice. Deletion of the α5 subunit of the GABA
A
Rs reduced the amnestic but not the sedative-hypnotic properties of etomidate. Thus, the amnestic and sedative-hypnotic properties of etomidate can be dissociated on the basis of GABA
A
R subtype pharmacology.
Abstract Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of ...patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials RCT, 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas.
Introduction: Patient selection is a challenge in designing effective phase I clinical trials in hematologic malignancies. Potential candidates typically have relapsed or refractory disease, and have ...had poor response to multiple prior lines of therapy. Such patients are at risk for early death, which reduces both the scientific yield and the therapeutic value of clinical trials: patients whose disease has already entered a terminal phase, and who subsequently die within a few months, provide little meaningful data to advance the understanding of an experimental treatment, and likely derive little clinical benefit from that treatment.
Currently, eligibility criteria for most trials rely on ad hoc laboratory thresholds, and on subjective assessments of performance status and life expectancy. It is desirable to have an objective, statistically validated means of predicting survival, to optimize patient selection for phase I clinical trials. A prognostic scoring system for this purpose has been developed and validated for patients with solid tumors (Garrido-Laguna et al. Cancer . 2012;118(5):1422-1428); this model incorporates variables on tumor type and number of metastatic sites, which are not directly applicable outside of solid tumors. Similar work has recently been reported in hematologic malignancies (Benajiba et al. Anti-cancer drugs . 2017;28(5):540-545), using only three variables: performance status, serum albumin, and disease class. We developed a novel prognostic scoring system to estimate progression free (PFS) and overall (OS) survival for patients enrolled in phase I clinical trials for treatment of hematologic malignancy.
Methods: We retrospectively reviewed the electronic medical records of 106 patients enrolled in phase I clinical trials for treatment of hematologic malignancies at the UT Health San Antonio Cancer Center between 2000 and 2014. Descriptive, univariate, and multivariate analyses were performed to determine the parameters that carry prognostic significance. Cox proportional hazards regression models of Progression Free and Overall Survival (PFS, OS) were used for multivariate analyses. A backward elimination process with a relaxed P-value (0.2) threshold was used to select variables for adjustment.
Results: Our analysis identified Hispanic ethnicity (P=0.03), low albumin level (<3.5 g/dL), low hemoglobin (<10 g/dL, P=0.02), hyperbilirubinemia (>1.0 mg/dL, P=0.03), abnormal white blood cell count (<4 k/µL or >10 k/µL, P<0.01), elevated lactate dehydrogenase (LDH) (>240 IU/L, P<0.01), and diagnosis of acute leukemia (P<0.01) as independent predictors of poor overall survival. The patient cohort was stratified by risk score into good (0-1), intermediate (2-4), and poor (5-7) risk categories, which were compared with respect to PFS and OS using Kaplan-Meier curves and log rank testing (see figures 1 and 2).
Conclusion: A simple score incorporating diagnosis, ethnicity, albumin, hemoglobin, bilirubin, white blood count, and LDH can identify patients with advanced hematologic malignancy who are likely to have short OS and PFS. Efforts are underway to validate this score against a separate cohort of phase I patients. Once validated, it could be incorporated in phase I trial design, potentially making these trials easier, faster, and more cost-effective to conduct, while allocating experimental treatments to those patients most likely to derive benefit.
Display omitted
No relevant conflicts of interest to declare.
Descripció osteològica del rorqual comú (Balaenoptera physalus, Linnaeus, 1758) del Museu de Ciències Naturals de Barcelona
Es presenta la descripció osteològica de l’esquelet del rorqual comú (MZB ...83-3084 Balaenoptera physalus, L.) del Museu de Ciències Naturals de Barcelona (MCNB). L’espècimen procedeix d’un encallament a Llançà (Alt Empordà) l’any 1862. L’esquelet pesa 1.161,59 kg i mesura 14,6 m, tot i que aquest valor no es correspon amb la longitud total de l’animal viu atès que no inclou la longitud del teixit intervertebral. L’esquelet reconstruït, incloent-hi el gruix del teixit intervertebral, assoleix una longitud de 17,35 m. El crani pesa 484 kg i té una longitud condilobasal de 431 cm que representa el 24,84% de la longitud total i que es correspon amb els valors mitjans obtinguts per a altres exemplars al Mediterrani. La columna vertebral consta de 58 vèrtebres estructurades segons la fórmula C7 T14 L14 Ca23 amb una longitud total de 10,29 m i un pes de 470,95 kg. Totes les vèrtebres cervicals estan lliures i mostren compressió dorsoventral a diferència de les vèrtebres toràciques, les lumbars i les primeres caudals que són relativament uniformes, de secció circular. A partir de la Ca14 es produeix un canvi en la forma de les vèrtebres i la relació entre l’amplada i l’altura és superior a 1, indicativa de compressió lateral. Ni a les epífisis de l’ulna i el radi ni a les de cap vèrtebra s’aprecien línies de sutura, la qual cosa indica que es tracta d’un exemplar adult que ha assolit la maduresa en el procés d’ossificació.
Description of the skeleton of the fin whale (Balaenoptera physalus, Linnaeus, 1758) at the Natural History Museum of Barcelona We describe the osteology of the fin whale (Balaenoptera physalus, L., ...registration code MZB 83-308) at the Natural History Museum of Barcelona. The specimen was stranded and died on a beach in Llançà (Girona, Spain) in 1862. The skeleton weighed 1,161.59 kg and measured 14. 6 m, although the live animal would have been longer because the invertebral tissue was not included in the length originally stated. The newly reconstructed skeleton includes the invertebral discs and is 17.5 m long. The skull weighs 484 kg and the condilobasal length is 431 cm ( 24. 84% of the total length), corresponding to the mean length of specimens in the Mediterranean. The vertebral column has 58 vertebra structured following the formula: C7 T14 L14 Cd23. It is 10.29 m long and weighs 470.95 kg. All the cervical vertebra are free and show dorsoventral compression, differing from the thoracic, lumbar and first caudal vertebra that are relatively uniform, and rounded. From Cd14 se onwards, the vertebra vary in shape and the relationship between width and height is greater than 1, indicating lateral compression. The lack of suture lines in the epiphysis of the ulna and radius indicates the specimen is an adult that has reached ossification maturation.
Se presenta la descripción osteológica del esqueleto del rorcual común (MZB 83-3084 Balaenoptera physalus, L.) del Museu de Ciències Naturals de Barcelona (MCNB). El espécimen procede de un ...varamiento en Llançà (Girona) en 1862. El esqueleto pesa 1.162,4 kg y mide 14,60 m. de largo. El esqueleto reconstruido con los discos intervertebrales, mide 18,3 m con un cráneo de 431cm. que representa el 23,5% de la longitud total y se corresponde con los valores medios obtenidos para otros ejemplares en el Mediterráneo. La columna vertebral posee 58 vértebras estructuradas según la fórmula: C7 T14 L14 Ca23 con una longitud total de 14 m. Todas las vértebras cervicales están libres y muestran compresión dorsoventral a diferencia de las vértebras torácicas, lumbares y primeras caudales que son relativamente uniformes, de sección circular. A partir de la Ca14 se produce un cambio en la forma de las vértebras y la relación entre la anchura y la altura es superior a 1 lo que indica una compresión lateral. El grado de osificación de las epífisis de la ulna y el radio, así como en todas las vértebras, no se aprecian líneas de sutura, indicando que se trata de un ejemplar adulto.
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