Depression symptom trends and health domains among lung cancer patients in the CanCORS study.

OBJECTIVES: Among lung cancer patients depression symptoms are common and impact outcomes. The aims of this study were to determine risk factors that contribute to persistent or new onset depression symptoms during lung cancer treatment, and examine interactions between depression symptoms and health domains that influence mortality. MATERIALS AND METHODS: Prospective observational study in five healthcare systems and 15 Veterans Affairs medical centers. Patients in the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium with lung cancer were eligible. The 8-item Center for Epidemiologic Studies Depression (CES-D) scale was administered at baseline and follow-up. Scores ≥4 indicated elevated depressive symptoms. Health domains were measured using validated instruments. We applied logistic regression and Cox proportional hazards modeling to explore the association between depression symptoms, health domains, and mortality. RESULTS: Of 1790 participants, 38% had depression symptoms at baseline and among those still alive, 31% at follow-up. Risk factors for depression symptoms at follow-up included younger age (OR=2.81), female sex (OR=1.59), low income (OR=1.45), not being married (OR=1.74) and current smoking status (OR=1.80); high school education was associated with reduced odds of depression symptoms at follow-up, compared with lesser educational attainment (OR=0.74) (all p values <0.05). Patients with depression symptoms had worse health-related quality of life, vitality, cancer-specific symptoms, and social support than patients without depression symptoms (all p<0.001). The association between depression symptoms and increased mortality is greater among patients with more lung cancer symptoms (p=0.008) or less social support (p=0.04). CONCLUSIONS: Patient risk factors for depression symptoms at follow-up were identified and these subgroups should be targeted for enhanced surveillance. Patients with depression symptoms suffer across all health domains; however, only more lung cancer symptoms or less social support are associated with worse mortality among these patients. These potentially modifiable health domains suggest targets for possible intervention in future studies.

Recent trends in testosterone testing, low testosterone levels, and testosterone treatment among Veterans.

Low serum testosterone (T) is common and increasingly prevalent with increased age. Recent studies report an 'epidemic' of T prescribing and concern about unnecessary T treatment. We investigated the number of men tested for T, the prevalence of low serum T levels, and initiation of T treatment among those with low T levels in men treated at Veterans Affairs (VA) facilities in the Northwest US (VISN 20). We identified male Veterans aged 40-89 years and examined yearly proportions of men tested for T, found to have low T levels (total T < 280 ng/dL, free T < 34 pg/mL, or bioavailable T < 84 ng/dL), and subsequently treated with T from 2002 to 2011. We excluded men who had T treatment in the year prior and men with diagnoses of prostate or breast cancer. Treatment initiation was defined as the first prescription for T within a year following a low T test. From 2002 to 2011, the yearly population of eligible men in VISN 20 increased from 129 247 to 163 572. The proportion of men who had serum T tests increased from 3.2% in 2002 to 5.8% in 2011. Among the tested men, the percentage of men with low T levels increased from 35.0 to 47.3%. However, the proportion of men with low T levels who were given T treatment within a year decreased from 31.0 to 28.0%. Despite large increases in T testing, and detection of men with low T levels, there was a slight decrease in the proportion of men with low T levels who were treated with T. The decrease in T treatment during this time period contrasts with other studies and may be related to higher comorbidity in Veterans and/or VA formulary restrictions on the use of transdermal T formulations.

Endoglucanase G from Fibrobacter succinogenes S85 belongs to a class of enzymes characterized by a basic C-terminal domain.

A 3.6-kb fragment of the Fibrobacter succinogenes S85 DNA was sequenced and found to contain two open reading frames (ORFs) on the same strand separated by 242 nucleotide bases. The translated protein from ORF1 had a predicted mass of 52.3 kDa. In a region of 320 amino acid overlap, it shares a 35% identity with the b-chain of the glutamate synthase of Escherichia coli. The ORF2 protein encodes a 519 residue protein designated CelG. It consists of an ORF of 1557 bp, encoding a polypeptide of 54.5 kDa. The N-terminal region, which contains the catalytic domain, is linked to a C-terminal basic domain, which has a predicted isoelectric point of 10.8. The catalytic domain in endoglucanase G (CelG) is homologous to the family 5 (A) cellulases. The enzyme has an apparent mass of 55 kDa, a pH optimum of 5.5, and temperature optimum of 25 degrees C. It had a specific activity of 16.5 mumols x min(-1) x mg-1 on barley b-glucan and produced a mixture of cellooligosaccharides from the hydrolysis of acid swollen cellulose and cellooligosaccharides. Antiserum raised against the purified form of CelG in E. coli failed to react with proteins from the native organism when grown on either glucose or crystalline cellulose, but reverse transcription and polymerase chain reaction techniques using RNA from the native organism demonstrated that the celG gene was expressed constitutively. Its distribution amongst subspecies of Fibrobacter was restricted to F. succinogenes S85.

Protease activities of rumen protozoa.

Intact, metabolically active rumen protozoa prepared by gravity sedimentation and washing in a mineral solution at 10 to 15 degrees C had comparatively low proteolytic activity on azocasein and low endogenous proteolytic activity. Protozoa washed in 0.1 M potassium phosphate buffer (pH 6.8) at 4 degrees C and stored on ice autolysed when they were warmed to 39 degrees C. They also exhibited low proteolytic activity on azocasein, but they had a high endogenous proteolytic activity with a pH optimum of 5.8. The endogenous proteolytic activity was inhibited by cysteine proteinase inhibitors, for example, iodoacetate (63.1%) and the aspartic proteinase inhibitor, pepstatin (43.9%). Inhibitors specific for serine proteinases and metalloproteinases were without effect. The serine and cysteine proteinase inhibitors of microbial origin, including antipain, chymostatin, and leupeptin, caused up to 67% inhibition of endogenous proteolysis. Hydrolysis of casein by protozoa autolysates was also inhibited by cysteine proteinase inhibitors. Some of the inhibitors decreased endogenous deamination, in particular, phosphoramidon, which had little inhibitory effect on proteolysis. Protozoal and bacterial preparations exhibited low hydrolytic activities on synthetic proteinase and carboxypeptidase substrates, although the protozoa had 10 to 78 times greater hydrolytic activity (per milligram of protein) than bacteria on the synthetic aminopeptidase substrates L-leucine-p-nitroanilide, L-leucine-beta-naphthylamide, and L-leucinamide. The aminopeptidase activity was partially inhibited by bestatin. It was concluded that cysteine proteinases and, to a lesser extent, aspartic proteinases are primarily responsible for proteolysis in autolysates of rumen protozoa. The protozoal autolysates had high aminopeptidase activity; low deaminase activity was observed on endogenous amino acids.

Proteolytic activity of rumen microorganisms and effects of proteinase inhibitors.

Proteolytic activity of the bovine rumen microflora was studied with azocasein as the substrate. Approximately 25% of the proteolytic activity of rumen contents was recovered in the strained rumen fluid fraction, and the balance of the activity was associated with the particulate fraction. The proportion of proteinase activity associated with particulate material decreased when the quantity of particulate material in rumen contents was reduced. The specific activity of the proteinase from the bacterial fraction was 6 to 10 times higher than that from the protozoal fraction. Proteinase inhibitors of synthetic, plant, and microbial origin were tested on proteolytic activity of the separated bacteria. Synthetic proteinase inhibitors that caused significant inhibition of proteolysis included phenylmethylsulfonyl fluoride, N-tosyl-1-lysine chloromethyl ketone, N-tosylphenylalanine chloromethyl ketone, EDTA, cysteine, dithiothreitol, iodoacetate, and Merthiolate. Plant proteinase inhibitors that had an inhibitory effect included soybean trypsin inhibitors types I-S and II-S and the lima bean trypsin inhibitor. Proteinase inhibitors of microbial origin that showed an inhibitory effect included antipain, leupeptin, and chymostatin; phosphoramidon and pepstatin had little effect. We tentatively concluded that rumen bacteria possess, primarily, serine, cysteine, and metalloproteinases.

Sulfide Production from Cysteine by Desulfovibrio desulfuricans.

Two rumen nitrate-reducing isolates of Desulfovibrio desulfuricans were found to hydrolyze cysteine with the production of sulfide and pyruvate. When cultured on agar medium containing yeast extract with nitrate as the primary electron acceptor and ferrous chloride as the indicator, blackening of colonies occurred. The blackening of colonies appeared sooner and was more intense when either cysteine or sulfate was added to the culture medium with nitrate present.

Nutritional characteristics of Megasphaera elsdenii.

Megasphaera elsdenii B159 (formerly Peptostreptococcus elsdenii; Rogosa 1971) is able to grow in a chemically defined medium containing minerals, NH4+ as the sole nitrogen source, sulfate as the source of sulfur, acetate and glucose as the carbon and energy sources, and the vitamins biotin, pyridoxine, and calcium pantothenate. When lactate serves as the carbon source, with cysteine present as the reducing agent, acetate is not required. Valine and threonine appeared to be required although direct inoculation of unwashed cells into media lacking these amino acids permitted growth in their absence after an extended incubation period. Sulfur sources utilized included sulfate, sulfide, thiosulfate, cysteine, and glutathionine; methionine was utilized less readily. When glucose was autoclaved in the medium, the generation time of M. elsdenii was 170--200 min, but increased to more than 400 min when glucose was autoclaved separately and added to the cooled sterile medium. When fructose, which had been sterilized separately, was utilized as the carbon and energy source, the generation time was 200 min.

Use of adenosine 5'-triphosphate as an indicator of the microbiota biomass in rumen contents.

A number of techniques were tested for their efficiency in extracting adenosine 5'-triphosphate (ATP) from strained rumen fluid (SRF). Extraction with 0.6 N H(2)SO(4), using a modification of the procedure described by Lee et al. (1971), was the most efficient and was better suited for extracting particulate samples. Neutralized extracts could not be stored frozen before assaying for ATP because large losses were incurred. The inclusion of internal standards was necessary to correct for incomplete recovery of ATP. The ATP concentration in rumen contents from a cow receiving a ration of dried roughage (mainly alfalfa hay) ranged from 31 to 56 mug of ATP per g of contents. Approximately 75% of the ATP was associated with the particulate material. The ATP was primarily of microbial origin, since only traces of ATP were present in the feed and none was found in "cell-free" rumen fluid. Fractionation of the bacterial and protozoal populations in SRF resulted in the isolation of an enriched protozoal fraction with a 10-fold higher ATP concentration than that of the separated rumen bacteria. The ATP pool sizes of nine functionally important rumen bacteria during the exponential phase of growth ranged from 1.1 to 17.6 mug of ATP per mg of dry weight. This information indicates that using ATP as a measure of microbial biomass in rumen contents must be done with caution because of possible variations in the efficiency of extraction of ATP from rumen contents and differences in the concentration of ATP in rumen microbes.