Characteristics and outcomes of hospitalised inpatients with indwelling urinary catheter-a retrospective study from a large regional hospital in Queensland.

BACKGROUND: Indwelling urinary catheters (IDCs) are a common invasive device in hospitalised patients. Their use is associated with increased risks of developing catheter associated urinary tract infections (CAUTI), and blood stream infections (BSI). AIMS: To examine the characteristics and outcomes of adult inpatients with an IDC inserted in hospital and identify risk factors for developing CAUTI and BSI. METHODS: We performed a retrospective observational study of 430 patients with IDC admitted to medical and surgical units of a leading (tertiary) hospital between Nov 2019 till April 2020. Multiple logistic regression analysis was performed to determine independent risk factors for developing urinary tract infection and blood stream infection. RESULTS: The prevalence of CAUTI in our study was 7.4%. Results of multiple logistic regression indicated that with each day of IDC in situ, the likelihood of UTI development increased by 9% (OR 1.09; 95% CI 1.00 to 1.18; p = 0.03). Age, gender, and catheter reinsertion were not associated with UTI development. CONCLUSIONS: Longer duration of IDC was associated with elevated risk of developing CAUTI. CAUTI rates were higher than some of those previously published. There was no statistical significance in frequency of CAUTI between medical and surgical patients. No statistically significant variables that contributed to the development of BSI were found. Interventions targeted at reducing catheter days should be used to improve CAUTI rates.

A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma.

BACKGROUND: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. PATIENTS AND METHODS: Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). RESULTS: A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. CONCLUSIONS: nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.

The proteasome activator 11 S regulator or PA28. Contribution By both alpha and beta subunits to proteasome activation.

The proteasome 11 S regulator (REG) consists of two homologous subunits, REGalpha and REGbeta. Each subunit is capable of activating the proteasome, and when combined, they form superactive REGalpha/REGbeta complexes. We have previously shown that a highly conserved loop in the REGalpha crystal structure is critical for proteasome activation. We now show that hetero-oligomers formed from REGalpha activation loop mutants and wild-type REGbeta or vice versa are partially active. By contrast, hetero-oligomers bearing mutations in the activation loops of REGalpha and REGbeta subunits are inactive, demonstrating that both alpha and beta subunits contribute to proteasome activation. We have also characterized REG proteins with mutations near or at their C termini. Partially active REGalpha(Y249C) and REGalpha(M247V) and an inactive REGalpha subunit bearing five additional C-terminal amino acids formed active hetero-oligomers with REGbeta. REGbeta subunits lacking 1, 2, or 9 C-terminal amino acids did not bind or activate the proteasome, but each of these mutants formed partially active hetero-oligomers with the monomer REGalpha(N50Y). However, hetero-oligomers formed from REG subunits lacking the last 14 amino acids were unable to bind the proteasome. Thus, C-terminal regions of both alpha and beta subunits are required for hetero-oligomers to bind the proteasome.

Proteasome activation by REG molecules lacking homolog-specific inserts.

The peptidase activities of eukaryotic proteasomes are markedly activated by the 11 S REG or PA28. The three identified REG subunits, designated alpha, beta, and gamma, differ significantly in sequence over a short span of 15-30 amino acids that we call homolog-specific inserts. These inserts were deleted from each REG to produce the mutant proteins REGalphaDeltai, REGbetaDeltai, and REGgammaDeltai. The purified recombinant proteins were then tested for their ability to oligomerize and activate the proteasome. Both REGalphaDeltai and REGgammaDeltai formed apparent heptamers and activated human red cell proteasomes to the same extent as their full-length counterparts. By contrast, REGbetaDeltai exhibited, at low protein concentrations, reduced proteasome activation when compared with the wild-type REGbeta protein. REGbetaDeltai was able to form hetero-oligomers with a single site, monomeric REGalpha mutant and with REGalphaDeltai. At low concentrations, the REGalphaDeltai/REGbetaDeltai hetero-oligomers stimulated the proteasome less than REGalpha/REGbeta oligomers formed from wild-type subunits, and the reduced activation by REGalphaDeltai/REGbetaDeltai was due to removal of the REGbeta insert, not the REGalpha insert. These studies demonstrate that the REGalpha and REGgamma inserts play virtually no role in oligomerization or in proteasome activation. By contrast, removal of REGbeta insert reduces binding of this subunit and REGalpha/REGbeta oligomers to proteasomes. On the whole, however, our findings show that REG inserts are not required for binding and activating the proteasome. We speculate that they serve to localize REG-proteasome complexes within cells, possibly by binding components in endoplasmic reticulum membranes.

Identification of an activation region in the proteasome activator REGalpha.

Proteasomes can be markedly activated by associating with 19S regulatory complexes to form the 26S protease or by binding 11S protein complexes known as REG or PA28. Three REG subunits, alpha, beta, and gamma, have been expressed in Escherichia coli, and each recombinant protein can activate human proteasomes. Combining PCR mutagenesis with an in vitro activity assay, we have isolated and characterized 36 inactive, single-site mutants of recombinant REGalpha. Most are monomers that produce functional proteasome activators when mixed with REGbeta subunits. Five REGalpha mutants that remain inactive in the mixing assay contain amino acid substitutions clustered between Arg-141 and Gly-149. The crystal structure of the REGalpha heptamer shows that this region forms a loop at the base of each REGalpha subunit. One mutation in this loop (N146Y) yields a REGalpha heptamer that binds the proteasome as tightly as wild-type REGalpha but does not activate peptide hydrolysis. Corresponding amino acid substitutions in REGbeta (N135Y) and REGgamma (N151Y) produce inactive proteins that also bind the proteasome and inhibit proteasome activation by their normal counterparts. Our studies clearly demonstrate that REG binding to the proteasome can be separated from activation of the enzyme. Moreover, the dominant negative REGs identified here should prove valuable for elucidating the role(s) of these proteins in antigen presentation.

Content of physician referrals to physical therapists at clinical education sites in Indiana.

BACKGROUND AND PURPOSE: The content of physician referrals to physical therapists was studied as an indicator of the level of decision making required of physical therapists. SUBJECTS AND METHODS: Seventeen managers of clinical education sites in Indiana provided diagnosis and treatment information on a total of 2,267 patient referrals. RESULTS: Differential diagnoses were specified in 39.6% of the referrals, and specific treatment orders were present in 32.6% of the referrals. Outpatient referrals contained significantly fewer diagnoses (29.1%) and specific orders (28.2%) than did inpatient referrals (56.0% and 39.5%, respectively). CONCLUSION AND DISCUSSION: These results indicate that physical therapists working in clinical education sites in Indiana must frequently exercise independent decision-making skills in determining the nature of the patient complaint and the appropriate treatment for the complaint. Academic programs that choose to expose students to a full range of decision-making situations should ensure a balance between inpatient and outpatient experiences.

Relationship between forward head posture and diagnosed internal derangement of the temporomandibular joint.

The purpose of this study was to determine if a sample of patients with internal derangement of the temporomandibular joint had a significantly greater amount of forward head posture than did an age- and gender-matched control group. Twenty-two patients at a single head, neck, and temporomandibular joint treatment center, who had the diagnosis of internal derangement of the temporomandibular joint, were compared with a control group of volunteers. The angle of each patient's head position was measured from four photographs (two of the patient sitting and two of the patient standing) with a diagonal line drawn from the spinous process of the seventh cervical vertebra to the tragus of the ear and a horizontal line drawn perpendicular to a plumb line suspended from the ceiling. The angles measured from each of the four photographs were averaged, and this figure was paired with that generated from an age- and gender-matched person in the control group. Results indicated that there was not a significantly greater degree of forward head posture in the experimental group.

Nutritional, physiological, genetic, sex, and age effects on fat-free dry matter composition of the body in avian, fish, and mammalian species: a review.

The purpose of this review is to outline and interpret the effects of nutrition, physiological state, sex, genetics, and age on composition of the fat-free dry matter of birds, mammals, and fishes in order to test the hypothesis that the protein:ash ratio in the body is constant. Calculations from a broad array of published data revealed that nutritional factors, including mineral, protein and amino acid nutriture, frequency and level of feeding, and energy intake and nonnutritional factors, including physiological state, sex, genetic background, and age of animal, may each alter the ratio of protein:ash in the body. All or part of the response may be associated with changes in accretion of body protein and(or) skeletal development and mineralization imposed by these nutritional and nonnutritional factors. In most cases of amino acid or protein deficiency, the protein:ash ratio was decreased relative to the control because the deposition of protein in muscle and viscera was reduced more than the growth and mineralization of the skeleton. In other cases, the protein:ash ratio was increased relative to a control because the dietary Ca or P intake or absorption limited skeletal mineralization. More knowledge is needed of how skeletal development and protein:ash ratio in the body is regulated, especially under the influence of nutritional, ontogenetic, and physiological variables among different genotypes of mammals, birds, and fishes. Documentation that the protein:ash ratio in the whole body of representative mammals, birds, and fishes is not constant, but is subject to manipulation, has important physiological and economic implications for developing food animals for the efficient production of lean meat.

Effects of additional feed during late gestation on reproductive performance of sows: a cooperative study.

A cooperative research study involving 1,080 litters was conducted at eight stations to determine the effects of additional feed during the last 23 d of gestation on reproductive performance of sows and on preweaning performance of their pigs. Primiparous and multiparous sows were fed fortified corn- or sorghum-soybean meal diets (14% crude protein). Control sows received 1.82 kg/d from March through November and 2.27 kg/d from December through February. Treated sows were fed an additional 1.36 kg of feed/d from d 90 of gestation to farrowing. Sows were allowed to consume the same diet ad libitum during a 21-d lactation. Additional feed in late gestation resulted in greater (P less than .001) sow weight gain from d 90 to d 110 of gestation (16.8 vs 9.0 kg) and greater (P less than .001) parturition-lactation weight loss (21.3 vs 16.4 kg). Total weight gain from breeding to 21 d of lactation favored sows that received extra feed (27.5 vs 22.7 kg; P less than .001). Sows receiving extra feed had more live pigs at farrowing (10.05 vs 9.71, P = .06) and at 21 d postpartum (8.35 vs 8.06, P = .09), and the pigs were heavier at birth (1.48 vs 1.44 kg, P = .003) and at 21 d (5.37 vs 5.20 kg, P = .006). Lactation feed intake and number of days from weaning to estrus were not affected by treatment. The results indicate that additional feed in late gestation improves reproductive performance in sows. In this study, the cost of an additional 31 kg of feed/sow was more than offset by the value of the additional sow weight gain (approximately 5 kg), the additional .3 of a pig/litter at weaning and the additional 2.6 kg of total litter weaning weight.

Excess crude protein for nongravid gilts.

Twenty-five nongravid crossbred gilts (avg initial wt, 126 kg) were placed on either a high (38%) or a low (13%) crude protein (CP) diet and fed either at the rate of 1.82 kg/d or had ad libitum access to feed. In addition, a fifth group was pair-fed the 13% CP diet to the average intake of the gilts fed high CP ad libitum. The experimental period lasted 30 d. Corn-soybean meal diets were used and CP levels were varied by altering the corn:soybean meal ratio. Gain and gain/feed were reduced (P less than .01) in gilts fed 1.82 kg/d compared with the gilts fed ad libitum or pair-fed gilts. Gain (P less than .03) and feed intake (P less than .01) of gilts with ad libitum access to the 13% CP diet were higher than those of gilts with ad libitum access to the 38% CP diet. Gain/feed was not different (P greater than .10) between the two groups, however. Rate of gain and feed efficiency of gilts pair-fed the 13% CP diet were similar (P greater than .10) to those of gilts with ad libitum access to the 38% CP diet. Plasma total free amino acids, NH3 and total protein were not (P greater than .10) affected by treatment. Plasma urea-N and urinary total N, urea-N and orotic acid were increased (P less than .01) in gilts fed the high CP diet regardless of feed intake level. However, urinary NH3 was higher (P less than .01) in gilts fed the low-protein diet. These results indicate that excess dietary CP for nongravid gilts decreases gain and feed intake and has no effect on efficiency of feed utilization, but it increases plasma urea-N and urinary total N, urea-N and orotic acid.

Ammonium polyphosphate as a source of phosphorus and nonprotein nitrogen for monogastrics.

Ammonium polyphosphate (APP) was substituted for 0, 50 and 100% of the P supplied by defluorinated rock phosphate (DRP) in corn-soybean meal diets for growing rats and growing-finishing (G-F) pigs. The diets were formulated to contain 10% protein, .75% Ca and .60% P. Two-thirds of the P in the control diet was supplied by DRP. Replacement of 50 or 100% of the DRP with APP increased the dietary N by 7.25 and 14.5%, respectively. To evaluate nonprotein N (NPN) utilization, we used ammonium chloride (NH4Cl) to provide a level of N equivalent to that supplied by APP when it replaced 100% of the P supplied by DRP. These four treatments were repeated with supplementation of limiting amino acids (L-lysine, L-tryptophan and DL-methionine. Daily feed intake, rate of gain and feed:gain (F:G) of rats and G-F pigs were not influenced (P greater than .05) by the substitution of APP for DRP as a P source in corn-soybean meal diets with or without supplemental amino acids. F:G was improved (P less than .05) by the addition of limiting amino acids to diets for pigs, and a similar trend occurred in rats. The addition of NH4Cl to the 10% protein diets as a source of NPN resulted in no observable benefit for growing rats or G-F pigs. Percentages of ham and loin, percentages of bone ash and P content of the bone ash in pigs were not influenced by the dietary treatments.

Use of deuterium oxide for the in vivo prediction of body composition in female rats in various physiological states.

Deuterium oxide (D2O) was used to estimate total body water (TBW) and subsequently to predict the body composition of female rats at breeding, after pregnancy and after lactation as influenced by dietary manipulation. The correlation between D2O space (grams) and body water (grams) was 0.893 (P < 0.01). Deuterium oxide space accounted for 70% of the variance in predicting the weight of TBW. Fixed effects (pregnancy, lactation, feeding levels and two-way interactions) accounted for an additional 10% (P < 0.05) of the variance. The correlation between TBW in grams (predicted from D2O space, grams) and total body protein (grams) was 0.700 (P < 0.01). Total body water accounted for 49% of the variance in total body protein. Fixed effects accounted for an additional 21% (P < 0.05) of the variance in total weight of body protein. The correlations between D2O space (%) and body water (%) and between D20 space (%) and body fat (%) were 0.786 (P < 0.01) and -0.758 (P < 0.01), respectively. The accuracy of estimation of body water (%) and body fat (%) from D2O space was not significantly improved (P > 0.05) when the fixed effects (pregnancy, lactation, feeding levels and two-way interactions) were included in the model.

Effect of energy intake during pregnancy and lactation on body composition in rats.

A paired feeding experiment involving high (H) and low (L) feeding levels during pregnancy and lactation was conducted using bred and open female rats to determine the effects on body composition. Pregnant rats contained a higher percentage of water in the fat-free body (FFB) than that of non-pregnant rats indicating tissue hydration. Composition of the FFB and fat-free dry matter (FFDM) was not altered by feeding level during pregnancy. During lactation, the feeding levels were either continued H-H and L-L or were changed to H-L or L-H within the lactating or open (non-lactating) pairs. Composition of the FFB and of the FFDM was altered by feeding level during lactation. A high energy intake result in a greater proportional loss of ash than of protein during lactation. In contrast, neither the composition of FFB nor FFDM was altered in the non-lactating rats on similar energy intake regimes. The lactating females had a higher percentage of water in FFB than the non-lactating rats. Although there was variation in water content of FFB and in the composition of FFDM, the correlation between percentage of body water and body fat after the adjustment of effects of pregnancy, lactation, energy and their interaction, was high (r = -0.98).

Nutrition and management of early weaned pigs: effect of increased nutrient concentrations and (or) supplemental liquid feeding.

Four experiments involving a total of 304 crossbred pigs weaned at 3 to 4 weeks of age were conducted to examine the effect of feeding supplemental liquid milk two to three times daily at weaning and (or) of altering the nutrient composition of the weaning diet. In addition, the effects on postweaning performance of preconditioning young pigs to supplemental milk feeding in the farrowing house were determined. Performance immediately postweaning was poor and was characterized by low weight gains and low feed intakes for approximately 7 days. Increasing the protein and (or) energy concentrations in the weaning diet had no beneficial effect on pig performance in Exp. 1. Feeding supplemental cow's milk three times daily for 4 days postweaning and (or) adding fat to the dry weaning diet also had no beneficial effect on pig performance in Exp. 2. An added milk product to the diet did tend to improve feed efficiency in this experiment. In the third experiment, performance was not affected by supplemental liquid milk feeding three times daily for 7 days and twice daily for an additional 7 days. Additions of 30% nonfat dried milk to the dry diet offered ad libitum did result in improvement in pig performance. Preconditioning of young pigs to supplemental liquid feeding while still nursing the sow resulted in no beneficial response in pig performance immediately postweaning in Exp. 4.

Ammoniation of corn contaminated with aflatoxin and its effects on growing rats.

Corn naturally contaminated with 2,000 ppb total aflatoxin was adjusted to 17% moisture and ammoniated (Am) with 1.5% (w/w) anhydrous ammonia in an attempt at detoxification. The ammonia treatment reduced the detectable concentration to 510 ppb total aflatoxins. Ninety-six male Sprague-Dawley rats (75 g avg) were randomly divided into eight treatment groups with 12 rats per treatment. A fortified 12%-protein corn-soybean meal diet served as the control (C) diet. The corn used in the C diet contained no detectable aflatoxin. Treatment 2 contained 1,670 ppb aflatoxin; treatments 3 and 4 were similar to treatments 1 and 2, respectively, except the corn used was ammoniated. Treatments 5 through 8 contained 830, 420, 210 and 100 ppb total aflatoxin, respectively. Liver weights expressed as a percentage of final live weight were increased (P less than .05) in rats consuming diets containing 1,670 ppb aflatoxin compared to the other treatments. Serum albumin, IgG and IgM concentrations were not affected by ammoniation or by concentration of aflatoxin in the corn. At the end of 4 weeks, total serum protein was increased (P less than .05) in rats consuming diets containing aflatoxin-contaminated (AfC) corn and Am corn compared to those consuming the C diet. Average daily gain and average daily feed consumption were reduced (P less than .01) in rats consuming the diet containing 1,670 ppb aflatoxin. The growth of rats consuming AfC corn that was Am was equal to that of rats consuming a similar concentration of aflatoxin by dilution. From these results and the results of others, it appears that ammoniation of corn contaminated with aflatoxin may be a practical and economical method for detoxification.