Characterization of nutrient runoff from perennial and annual forages following broiler litter application.

Information on how forage species influence sediment and nutrient transport in runoff is required for limiting non-point source pollution from broiler litter applications. In this study, we examined the effects of five forage species (eastern gamagrass [Tripsacum dactyloides (L.) L.], Kernza [Thinopyrum intermedium (Host) Barkworth & D.R. Dewey], silphium [Silphium integrifolium Michx.], switchgrass [Panicum virgatum L.], and winter wheat [Triticum aestivum L.]) on runoff nutrient losses from broiler litter-amended (5.6 Mg ha-1 ) and non-amended plots (control) following four simulated rainfall (5 cm h-1 ) events that were applied to these plots in late spring and early fall of 2019 and 2021. Runoff collected for 30 min was analyzed for total suspended solids (TSS) and nutrients (total organic carbon [TOC], soluble reactive phosphorus [SRP], total dissolved phosphorus [TDP], total phosphorus [TP], total nitrogen [TN], ammonium-nitrogen [NH4 -N], and nitrate-nitrogen [NO3 -N]). Total sediment and nutrient losses increased 5- to 19-fold following litter application for all species, which reduced to background levels during fall rainfall events. Across the four simulated rainfall events, switchgrass resulted in lower cumulative losses of TSS, TOC, SRP, TDP, TP, and NO3 -N than gamagrass and wheat but did not differ from Kernza and silphium for litter-amended treatments. The performance of newly introduced perennial crops (Kernza and silphium) was similar or better than that of gamagrass in terms of cumulative runoff sediment and nutrient losses. Results show high potential for Kernza, silphium, and switchgrass to improve water quality when used in forage-vegetative filter strip systems.

Cell salvage as part of a blood conservation strategy in anaesthesia.

The use of intraoperative cell salvage and autologous blood transfusion has become an important method of blood conservation. The main aim of autologous transfusion is to reduce the need for allogeneic blood transfusion and its associated complications. Allogeneic blood transfusion has been associated with increased risk of tumour recurrence, postoperative infection, acute lung injury, perioperative myocardial infarction, postoperative low-output cardiac failure, and increased mortality. We have reviewed the current evidence for cell salvage in modern surgical practice and examined the controversial issues, such as the use of cell salvage in obstetrics, and in patients with malignancy, or intra-abdominal or systemic sepsis. Cell salvage has been demonstrated to be safe and effective at reducing allogeneic blood transfusion requirements in adult elective surgery, with stronger evidence in cardiac and orthopaedic surgery. Prolonged use of cell salvage with large-volume autotransfusion may be associated with dilution of clotting factors and thrombocytopenia, and regular laboratory or near-patient monitoring is required, along with appropriate blood product use. Cell salvage should be considered in all cases where significant blood loss (>1000 ml) is expected or possible, where patients refuse allogeneic blood products or they are anaemic. The use of cell salvage in combination with a leucocyte depletion filter appears to be safe in obstetrics and cases of malignancy; however, further trials are required before definitive guidance may be provided. The only absolute contraindication to the use of cell salvage and autologous blood transfusion is patient refusal.

Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets.

Triple negative breast cancers (TNBCs) have a relatively poor prognosis and cannot be effectively treated with current targeted therapies. We searched for genes that have the potential to be therapeutic targets by identifying genes consistently overexpressed when amplified. Fifty-six TNBCs were subjected to high-resolution microarray-based comparative genomic hybridization (aCGH), of which 24 were subjected to genome-wide gene expression analysis. TNBCs were genetically heterogeneous; no individual focal amplification was present at high frequency, although 78.6% of TNBCs harboured at least one focal amplification. Integration of aCGH and expression data revealed 40 genes significantly overexpressed when amplified, including the known oncogenes and potential therapeutic targets, FGFR2 (10q26.3), BUB3 (10q26.3), RAB20 (13q34), PKN1 (19p13.12) and NOTCH3 (19p13.12). We identified two TNBC cell lines with FGFR2 amplification, which both had constitutive activation of FGFR2. Amplified cell lines were highly sensitive to FGFR inhibitor PD173074, and to RNAi silencing of FGFR2. Treatment with PD173074 induced apoptosis resulting partly from inhibition of PI3K-AKT signalling. Independent validation using publicly available aCGH data sets revealed FGFR2 gene was amplified in 4% (6/165) of TNBC, but not in other subtypes (0/214, P=0.0065). Our analysis demonstrates that TNBCs are heterogeneous tumours with amplifications of FGFR2 in a subgroup of tumours.

Effect of zinc supplementation on the morbidity, immune function, and growth of low-birth-weight, full-term infants in northeast Brazil.

In Brazil, the highest incidence of low birth weight (LBW) occurs in the northeast, and diarrhea and respiratory infections are the main causes of infant mortality and morbidity. We hypothesized that LBW infants may be zinc deficient, and that this might be adversely affecting their immune function, morbidity, and postnatal growth. We therefore examined the effect of zinc supplementation on these outcomes during the first 6 mo of life. LBW full-term infants (mean birth weight 2337 g) were given daily for 8 wk either 5 mg Zn (n = 71), 1 mg Zn (n = 68), or a placebo (n = 66). Morbidity was determined prospectively through daily home visits (except on Sunday) during weeks 0-8, then twice weekly in weeks 9-26. Anthropometric measurements were made at 0, 4, 8, 17, and 26 wk. Immune function was assessed at 8 wk by the phytohemagglutinin skin test. Supplementation (5 mg Zn) was associated with a 28% reduction in diarrhea prevalence over the 6-mo period [after adjustment for confounders (P = 0.043)], and a 33% reduction in the prevalence of cough (NS, adjusted prevalence P = 0.073). All infants had a positive immune response at 8 wk. Although supplementation had no significant effect on weight and length gains from 0 to 26 wk, infants given 5 mg Zn gained more weight than infants given placebo during weeks 17-26 (P = 0.024, analysis of variance). There was no effect on any outcome with 1 mg Zn. We conclude that 5 mg Zn/d is of benefit to LBW, full-term infants who only have a modest weight deficit.

Zinc supplementation, mental development and behaviour in low birth weight term infants in northeast Brazil.

OBJECTIVE: To test whether zinc supplementation reduces the deficits in mental development and behaviour that are found in term infants of low birth weight in the study population. DESIGN: A prospective double-blind, part-randomised efficacy trial. SETTING: A low-income population in Pernambuco, northeast Brazil, where the economy is largely dependent on sugar-cane production, and where over 90% of deliveries occur in health facilities. SUBJECTS: During a 20-month period, all singleton, term infants weighing 1500-2499 g born to families of low income ( < US $280/month) were enrolled at birth (n = 205). At 6 and 12-months, the numbers tested were 163 and 138 respectively. INTERVENTION: Infants born from January 1993-January 1994 were randomly assigned to receive daily, except Sundays, a placebo (n = 66) or 1 mg zinc (n = 68). Those born February-August 1994 were given 5 mg zinc (n = 71). Supplementation was for eight weeks, starting at birth. Field workers visited each infant at home to administer the supplement. RESULTS: At 6 and 12-months, mental and psychomotor development was assessed with the Bayley Scales of Infant Development and no significant differences in the scores of the three groups were found. At 12-months, behaviour was also assessed on 5 ratings. Ratings were highest in infants given 5 mg zinc (P = 0.042). CONCLUSIONS: Zinc supplementation (5 mg/d) for eight weeks may reverse some of the poor behaviours, particularly responsiveness, exhibited by low birth weight infants. No amelioration of their mental and psychomotor deficits was found.

PIP: Severe zinc deficiency, widespread in developing countries, has been associated with cognitive and psychomotor impairment in animal studies. The capability of zinc supplementation, to reduce the deficits in mental development and behavior found in low-birth-weight term infants, was assessed in a prospective study conducted in a low-income community in Pernambuco, Brazil. All 205 singleton, term infants, delivered at the local hospital in a 20-month period and weighing 1500-2499 g at birth, were enrolled. Infants born from January 1993 to January 1994, were randomly assigned to receive either a placebo (n = 66) or 1 mg of zinc (n = 68) 6 days a week. The 71 low-birth-weight infants delivered from February to August 1994, were given 5 mg of zinc 6 days a week. Supplementation administered by local health workers was initiated at birth and lasted for 8 weeks. Mental and psychomotor development was measured at 6 and 12 months of age by the Bayley Scales of Infant Development. There were no significant differences between infants in the 3 study groups on this test. Also at 12 months, infant behavior was assessed on 5 scales. Ratings for one of these scales (responsiveness to tester) were significantly higher in infants who received 5 mg of zinc than in the 2 other groups, and the 5 mg zinc group also had the highest scores on the 4 other scales. Further studies are urged to investigate the effect of zinc provided later in life, and for longer periods of time, on the development of low-birth-weight infants.

Severe malnutrition in children: high case-fatality rates can be reduced.

PIP: This article offers a protocol for reducing high case fatality rates from malnutrition. Most child deaths from malnutrition occur in the first few days of treatment. Treatment should involve stabilization followed by rehabilitation. The article describes the treatment procedures for hypoglycemia, hypothermia, dehydration, and missed infections and discusses feeding during the stabilization and rehabilitation phases of treatment. All severely malnourished children have excess body sodium but high intracellular and low plasma levels. Malnourished children have deficiencies of potassium and magnesium that may take 2 weeks to correct. Edema is partly due to deficiencies in potassium and magnesium. A high sodium intake can be corrected by rehydrating with a modified oral rehydration solution and the special starter formula. Family food should be prepared without salt. Magnesium and potassium should be added directly to foods. All severely malnourished children have vitamin and mineral deficiencies. Deficiencies may include vitamin A, zinc, copper, selenium, and folic acid. Multivitamin supplements can correct for micronutrient deficiencies. It is advised that zinc should not be ignored, since it is responsible for repair of intestinal mucosa, halting diarrhea, healing of ulcerated skin lesions, restoration of appetite, improved immune function, and lean tissue synthesis. Iron should not be given until growth starts, infections are controlled, and antioxidant status is improved (usually 1 week after admission). Early introduction of iron poses a risk of enhancing pathogen increases and stimulating production of toxic free radicals. Relapses can be reduced by training parents how to feed their child frequently with energy and nutrient dense foods. The regimen was tested in a South African project and found to reduce mortality from 30% to 20%. After greater hospital attention to treatment of sepsis and hypoglycemia, case fatality declined to 6%.^ieng

Low birth weight and morbidity from diarrhea and respiratory infection in northeast Brazil.

OBJECTIVE: To compare morbidity and mortality rates of low birth weight (LBW) and appropriate birth weight infants born at term, focusing on diarrheal and respiratory infections. STUDY DESIGN: A cohort of 133 LBW infants (1500 to 2499 gm) and 260 appropriate birth weight infants (3000 to 3499 gm), individually matched by sex and season of birth, were followed for the first 6 months of life. None had congenital anomalies and all were from poor families living in the interior of Pernambuco, northeast Brazil. Data on infant deaths, hospitalizations, and morbidity were collected prospectively through daily home visits (except Sundays) from birth through week 8, then twice weekly for weeks 9 to 26. The effects of birth weight were assessed with a variety of multivariable techniques, controlling for confounders. RESULTS: Of the LBW infants, 56% were wasted (thin), 23% were stunted, and 17% were both wasted and stunted. The LBW infants (median 2380 gm) experienced a sevenfold higher mortality rate and fourfold higher rate of hospitalization than appropriate birth weight infants. Almost all deaths and hospitalizations were in the postneonatal period. The LBW infants also experienced 33% more days with diarrhea and 32% more days with vomiting (p = 0.003 in each case). The prevalences of cough and fever were not significantly different. CONCLUSIONS: Infant deaths, hospitalizations, and diarrheal morbidity are increased in term LBW infants who have only a modest weight deficit.

PIP: During January-December 1993, in the interior of Pernambuco State, northeast Brazil, researchers recruited 133 low birth weight (LBW) (1500-2499 g) infants and 260 sex- and birth season-matched controls of appropriate birth weight (ABW) (3000-3499 g) from the maternity wards of hospitals in five communities. All infants were randomly assigned to receive either 1 mg zinc/day for 8 weeks or a placebo. All infants came from low income families. The researchers compared their morbidity, especially diarrhea and respiratory tract infections, and mortality rates during the first 6 months of life. Zinc supplement had no effect on any of the outcome measures. LBW infants were more likely than ABW infants to die (7.5% vs. 0.8%; adjusted hazard rate ratio [AHRR] = 6.58; p = .006) and to be hospitalized (24.8% vs. 6.5%; AHRR = 4.09; p .001) during the first 6 months of life. Yet the rate of consultations with medical personnel was essentially the same for both groups. 90% of the LBW deaths occurred in the postneonatal period, the underlying causes being diarrhea and respiratory infections. For both LBW and ABW infants, diarrhea was the main cause of hospitalization. Both groups experienced little diarrhea during the first 6 weeks of life. Thereafter, LBW infants suffered a higher prevalence of diarrhea than ABW infants up until 5 months. Beginning with day 1, LBW infants experienced more vomiting than ABW infants. Both groups experienced increasing rates of cough and fever throughout the 6-month period. Differences between the two groups were less pronounced than they were for diarrhea or vomiting. LBW infants were more likely to be sick longer with diarrhea and vomiting than ABW infants (p .001), but the difference in prevalence was less significant (p = .043). The onset of diarrhea was strongly associated with feeding mode (hazard rate ratio = 1.56 for partially breast-fed infants and 2.34 for infants no longer breast fed; p .001) as was the onset of vomiting (0.95 and 1.86, respectively; p .001 for the latter). LBW infants suffered more deaths, hospitalizations, and diarrhea morbidity than ABW infants.

Fighting malnutrition from hospital to home.

PIP: At a Children's Nutrition Unit in Bangladesh, a screening process has been developed to determine the type of care which should be provided to malnourished children. Malnourished children receive an initial period of full-time medical attention if they exhibit apathy and anorexia, dehydration, severe anemia, life-threatening infection, hypoglycemia, hypothermia, or severe Vitamin A deficiency. Also, malnourished children under 12 months old are given preference for in-patient care. Children may be hospitalized for three to five weeks until they are reasonable recovered and have reached a target weight-for-height or they may be discharged early and receive continued treatment through day care or home visits. Goals of the minimum stay (one to two weeks) should include restored appetite, treatment of clinical complications, and teaching the mother about appropriate feeding. Hospitalization and day care in the hospital may be very difficult for a family to manage. Home-based treatment, on the other hand, produces good, although slower, results and is the most cost-effective approach. Success of home care depends upon the quality of care and advice given during home visits by health personnel and an effective referral system if the children need more attention. In this program, while the provision of a Vitamin and mineral mixture is considered helpful, food supplements are not distributed. Even very poor families can adapt family foods to provide better nutrition. Less malnourished children also need attention, and their mothers must be trained to adapt family foods, give frequent meals, and continue to breast feed. Action is needed when growth begins to falter to prevent the need for later treatment. In Dhaka, the total cost to rehabilitate one child is US$29 for home-based care, US$59 for day care, and US$156 for in-patient care.^ieng

Why have mortality rates for severe malnutrition remained so high?

A review of the literature that has appeared over the past five decades indicates that the median case fatality from severe malnutrition has remained unchanged over this period and is typically 20-30%, with the highest levels (50-60%) being among those with oedematous malnutrition. A likely cause of this continuing high mortality is faulty case-management. A survey of treatment centres worldwide (n = 79) showed that for acutely ill children, inappropriate diets that are high in protein, energy and sodium and low in micronutrients are commonplace. Practices that could have fatal consequences, such as prescribing diuretics for oedema, were found to be widespread. Evidence of outmoded and conflicting teaching manuals also emerged. Since low mortality levels from malnutrition can be achieved using appropriate treatment regimens, updated treatment guidelines, which are practical and prescriptive rather than descriptive, need to be implemented as part of a comprehensive training programme.

An in vivo model of intratumoural aromatase using aromatase-transfected MCF7 human breast cancer cells.

About two-thirds of human breast carcinomas contain detectable levels of aromatase, the enzyme which converts androgens to oestrogens. Assessment of the importance of this enzyme to breast cancer growth has been hampered by the absence of an adequate model system. We have previously reported that MCF7 human hormone-dependent breast cancer cells transfected with human aromatase cDNA (Arom1 cells) showed a growth response in vitro to exogenous androgens and this effect was blocked by aromatase inhibitors. We report here our use of these cells to develop a xenograft model in athymic nude mice. Neither MCF7 cells nor Arom1 cells formed tumours in oophorectomised (ovx) nude mice unless provided with oestradiol (E2) support. Once established, Arom1, but not MCF7, tumours could be grown in ovx females supplemented with androstenedione (delta 4A). The mean plasma level of delta 4A was 14 nmol/L in supplemented animals and < 0.5 nmol/L in unsupplemented animals. Similarly, unsupplemented male nude mice were able to support the growth of Arom1 tumours but not MCF7 tumours. The potent and highly specific aromatase inhibitor CGS20267 (letrozole) significantly decreased tumour growth at 2 mg/kg/day and completely inhibited growth at 20 mg/kg/day in delta 4A-supplemented but not E2-supplemented animals. Our results indicate that delta 4A-dependent growth of Arom1 tumours in vivo is mediated through the action of intratumoural aromatase. This model should allow an assessment of the critical levels of aromatase required for tumour growth support.

Biological effects of stable overexpression of aromatase in human hormone-dependent breast cancer cells.

Aromatase is a key enzyme in the conversion of androstenedione and testosterone to oestrone and oestradiol. Intratumoral aromatase activity is expressed by around 70% of breast carcinomas, but it is not clear what effect this has on the tumour phenotype. To address this question we expressed human aromatase in hormone-dependent MCF-7 breast cancer cells. Clone Arom. 1 expressed aromatase at 1,000 times the endogenous level in wild-type (WT) cells. Clone Arom. 2 incorporated the expression construct but did not express aromatase at levels above WT. There was no morphological difference between the two clones and WT, all three cell lines expressed oestrogen receptor at equivalent levels, and all manifested a mitogenic response to oestradiol. In steroid-depleted medium Arom. 1 cells showed significant growth enhancement over WT and Arom. 2, and this growth advantage was increased by exogenous androstenedione or testosterone. Both the enzyme activity and androgen-stimulated growth of Arom. 1 cells were completely reversible by aromatase inhibitor CGS 16949A. The Arom. 1 cell line may contribute to the development of an in vivo model of intratumoral aromatase, to study the biological significance of this phenomenon.

Interventions for the control of diarrhoeal diseases among young children: prevention of low birth weight.

The effect of low birth weight (LBW) on diarrhoea morbidity and mortality is analysed and interventions to increase birth weights are reviewed. Birth weight is a major determinant of infant mortality and, in developed countries at least, its effect on neonatal mortality is independent of socioeconomic status. We have located no satisfactory data on LBW as a determinant of diarrhoea mortality or morbidity. The strong association between LBW and mortality, however, makes it likely that there is an association between LBW and diarrhoea mortality in developing countries where diarrhoea is a major cause of infant death. Poor maternal nutrition, certain infections, pre-eclampsia, arduous work after mid-pregnancy, short birth intervals, and teenage pregnancy are likely to be causally associated with LBW in developing countries. Tobacco and alcohol consumption are additional risk factors.Of the interventions examined, maternal food supplementation has been the most studied. If targeted to mothers at nutritional risk, and if the food is consumed in addition to the usual diet, the prevalence of LBW can be expected to be reduced. However, food supplementation can be expensive and the results from carefully supervised feeding trials may be better than those that can be achieved in national programmes. The effect of supplementation with iron, zinc or folate requires further study. If it were possible to intervene in maternal nutrition, health and life-style in a developing country in a way that reduced the prevalence of LBW from around 30% to around 15%, a fall in the infant mortality rate of around 26% would be expected. The fall in infant diarrhoea mortality rate might be similar. The scarce data on relative risk of morbidity by birth weight do not allow any comparable computations for morbidity reductions to be made.This review confirms that whatever its association with diarrhoea, LBW is an important determinant of infant mortality. For the more general goal of reducing infant mortality it is necessary to know more about the nature, etiology, and prevention of LBW in developing countries.