Child linear growth trajectories during the first three years of life in relation to infant iron status: a prospective cohort study in rural Vietnam.

BACKGROUND: Early childhood growth patterns have long-term consequences for health and disease. Little is known about the interplay between growth and iron status during childhood. We explored the interplay between linear growth and iron status during early childhood, by assessing child growth trajectories between 6 and 36 months (m) of age in relation to infant iron status at 6 months of age. METHODS: A cohort study of infants born to women who had previously participated in a cluster randomized controlled trial of antenatal micronutrient supplementation, conducted in rural Vietnam. The relationship between child linear growth trajectories and infant iron status (ferritin concentration) was examined using latent growth curve modeling. Primary outcomes were height for age z scores (HAZ) and growth trajectory between 6 and 36 m of age. RESULTS: A total of 1112 infants were included in the study. Mean [SD] HAZ scores decreased over time from -0·58 [0·94] at 6 m, to -0·97 [0·99] at 18 m, to -1·14 [0·89] at 36 m of age. There was a steep linear decline in the HAZ scores between 6 and 18 m of age, followed by a slower linear decline from 18 to 36 m of age. Ferritin concentration at 6 m of age was inversely associated with HAZ score at 6 m of age (-0·145, 95% CI [-0.189, -0.101]). There was no association between infant ferritin at 6 m of age and child growth trajectory between 6 and 36 m of age. CONCLUSIONS: Iron status at six months of age did not influence a child's later linear growth trajectory in this cohort of rural Vietnamese children. Longitudinal studies with repeated ferritin and height measurements are required to better delineate this relationship and inform public health interventions.

White hard clam (Meretrix lyrata) shells as novel filter media to augment the phosphorus removal from wastewater.

It is well recognized that filter media play a crucial role in constructed wetlands (CWs) for decontamination of phosphorus (P)-rich wastewater. This study investigates the suitability of raw white hard clam shells (WHC) and white hard clam shells thermally modified at 800 °C (WHC-M800) as potential media to enhance P treatment performance in CWs. The results indicated that both WHC and WHC-M800 displayed appropriate physicochemical properties, such as high porosity, excellent hydraulic conductivity, and rich Ca content. WHC-M800 exhibited a superior P adsorption capacity (38.7 mg/g) to WHC (12.8 mg/g). However, the practical utilization of WHC-M800 as filter media in CWs may be compromised, due to certain limitations, for example: extremely high pH values in the post-adsorption solutions; high weight losses during calcination and adsorption processes; low mechanical strength; and intensive energy consumption. In contrast, the WHC demonstrated significant advantages of reasonably high P adsorption capacity, locally abundant availability, low cost, and marginal side effects. The fractionation of inorganic P of WHC and WHC-M800 revealed that Ca-bounded P was the most dominant binding form, followed by loosely bound P, Fe-P, occluded P, and Al-P. The present study demonstrates that recycling of WHC shells as a potential substrate in CWs provides a feasible method for upgrading P removal in CWs. Additionally, it helps to reduce waste WHC shells in a simple, cheap, and eco-friendly way, thus can double environmental benefits.

Two-step system consisting of novel vertical flow and free water surface constructed wetland for effective sewage treatment and reuse.

This study developed a unique system by combining the novel vertical flow (NVF) using expanded clay (ExC) and free flow surface constructed wetland (FWS) for dormitory sewage purification and reuse. The NVF tank consisted of filter layers of ExC, sandy soil, sand, and gravel. The FWS consisted of sandy soil substrate and was installed after the NVF. Colocasia esculenta and Dracaena sanderiana was planted in NVF and FWS, respectively. The treatment system was operated and tested for more than 21 weeks by increasing the hydraulic loading rate (HLR) from 0.02 m/d to 0.12 m/d. The results demonstrated that effluents in the system changed proportionally to the HLRs, except for nitrate nitrogen. Furthermore, the maximum removal efficiencies for TSS, BOD5, NH4-N, and Tcol were 76 ± 13%, 74 ± 11%, 90 ± 3%, and 59 ± 18% (0.37 ± 0.19 log10MPN/100 mL), respectively. At HLRs of 0.04-0.06 m/d, the treatment system satisfied the limits of agriculture irrigation.

Effect of low-dose versus higher-dose antenatal iron supplementation on child health outcomes at 36 months of age in Viet Nam: longitudinal follow-up of a cluster randomised controlled trial.

INTRODUCTION: Intermittent iron-folic acid supplementation (IFA) is currently recommended for pregnant women in populations where anaemia prevalence among pregnant women is <20% or if daily iron is not acceptable. The effect of providing lower doses of antenatal elemental iron through intermittent regimes on longer-term health outcomes in childhood is unclear. METHODS: A prospective cohort study conducted between May 2012 and May 2014 in Viet Nam among children of 36 months of age, born to women previously enrolled in a cluster randomised controlled trial of antenatal micronutrient supplementation (daily IFA (60 mg elemental iron) vs twice-weekly IFA (60 mg elemental iron) vs twice-weekly multiple micronutrient (MMN) supplementation (60 mg elemental iron)). Primary outcomes were height-for-age z-scores (HAZ), according to WHO growth standards and cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) at 36 months of age. RESULTS: A total of 1017 children born to mothers enrolled in the cluster randomised trial were assessed at 36 months of age. Adjusted mean differences (MDs) in HAZ were -0.14 (95% CI -0.28 to -0.01) and -0.15 (95% CI -0.29 to -0.01) in children born to mothers who received twice-weekly IFA or MMN compared with those who received daily IFA. Children born to mothers who received twice-weekly MMN had lower composite motor scores compared with those who received daily IFA (MD -2.07, 95% CI -4.11 to -0.03). There were no differences in composite cognitive scores in the twice-weekly compared with daily regimens. CONCLUSIONS: Low-dose antenatal IFA supplementation (120 mg elemental iron per week) resulted in lower HAZ and motor composite scores in children compared with higher-dose antenatal IFA supplementation (420 mg elemental iron per week). This highlights the importance of adequate iron stores during pregnancy and the need for careful monitoring when lower-dose antenatal iron regimens are used. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry: 12610000944033.

Adjunctive yoga v. health education for persistent major depression: a randomized controlled trial.

BACKGROUND: The objective of this study was to determine whether hatha yoga is an efficacious adjunctive intervention for individuals with continued depressive symptoms despite antidepressant treatment. METHOD: We conducted a randomized controlled trial of weekly yoga classes (n = 63) v. health education classes (Healthy Living Workshop; HLW; n = 59) in individuals with elevated depression symptoms and antidepressant medication use. HLW served as an attention-control group. The intervention period was 10 weeks, with follow-up assessments 3 and 6 months afterwards. The primary outcome was depression symptom severity assessed by blind rater at 10 weeks. Secondary outcomes included depression symptoms over the entire intervention and follow-up periods, social and role functioning, general health perceptions, pain, and physical functioning. RESULTS: At 10 weeks, we did not find a statistically significant difference between groups in depression symptoms (b = -0.82, s.e. = 0.88, p = 0.36). However, over the entire intervention and follow-up period, when controlling for baseline, yoga participants showed lower levels of depression than HLW participants (b = -1.38, s.e. = 0.57, p = 0.02). At 6-month follow-up, 51% of yoga participants demonstrated a response (⩾50% reduction in depression symptoms) compared with 31% of HLW participants (odds ratio = 2.31; p = 0.04). Yoga participants showed significantly better social and role functioning and general health perceptions over time. CONCLUSIONS: Although we did not see a difference in depression symptoms at the end of the intervention period, yoga participants showed fewer depression symptoms over the entire follow-up period. Benefits of yoga may accumulate over time.

Impact of High-Level Daptomycin Resistance in the Streptococcus mitis Group on Virulence and Survivability during Daptomycin Treatment in Experimental Infective Endocarditis.

Among the viridans group streptococci, the Streptococcus mitis group is the most common cause of infective endocarditis. These bacteria have a propensity to be ß-lactam resistant, as well as to rapidly develop high-level and durable resistance to daptomycin (DAP). We compared a parental, daptomycin-susceptible (DAPs) S. mitis/S. oralis strain and its daptomycin-resistant (DAPr) variant in a model of experimental endocarditis in terms of (i) their relative fitness in multiple target organs in this model (vegetations, kidneys, spleen) when animals were challenged individually and in a coinfection strategy and (ii) their survivability during therapy with daptomycin-gentamicin (an in vitro combination synergistic against the parental strain). The DAPr variant was initially isolated from the cardiac vegetations of animals with experimental endocarditis caused by the parental DAPs strain following treatment with daptomycin. The parental strain and the DAPr variant were comparably virulent when animals were individually challenged. In contrast, in the coinfection model without daptomycin therapy, at both the 106- and 107-CFU/ml challenge inocula, the parental strain outcompeted the DAPr variant in all target organs, especially the kidneys and spleen. When the animals in the coinfection model of endocarditis were treated with DAP-gentamicin, the DAPs strain was completely eliminated, while the DAPr variant persisted in all target tissues. These data underscore that the acquisition of DAPr in S. mitis/S. oralis does come at an intrinsic fitness cost, although this resistance phenotype is completely protective against therapy with a potentially synergistic DAP regimen.

Starch gelatinization and in vitro digestibility behaviour after heat treatment: Comparison between plantain paste and piece of pulp.

Over the 65-100°C range and at a water content of 1.6kgkg(-1)db, a comparison was conducted between plantain paste (dispersion made of flour and water) and pulp pieces after cooking to evaluate their respective degree of starch gelatinization (α) and in vitro digestibility. Below 76°C and at 100°C, the gelatinization behaviour of starch into pulp pieces and paste was similar, whereas at 85°C a significant mean relative difference was observed in between. For α in the 0-1 range, pieces of plantain pulp exhibited a lower rapidly digestible starch fraction (30%) and a higher resistant starch fraction (33%) than the flour paste, suggesting some structural effects. Both Weibull and exponential models showed a good fit for α over temperature range and starch digestibility fractions over α. Although no explicit relationship was established between the intact pulp structure and grinded flour state of plantain, the evaluation of the degree of starch gelatinization and digestibility of a plantain flour paste, could be used to predict the gelatinization and digestibility behaviour of plantain starch in entire pieces of pulp.

Exclusive breast feeding in early infancy reduces the risk of inpatient admission for diarrhea and suspected pneumonia in rural Vietnam: a prospective cohort study.

BACKGROUND: Acute respiratory infections and diarrhea remain the leading causes of infant morbidity and mortality, with a high burden of both pneumonia and diarrhea in South-East Asia. The aim of the study was to determine antenatal and early infant predictive factors for severe morbidity episodes during the first 6 months of life in Ha Nam province, Vietnam. METHODS: A prospective cohort study of 1049 infants, born to women who had previously participated in a cluster randomized controlled trial of antenatal micronutrient supplementation in rural Vietnam, was undertaken between 28th September 2010 and 8th Jan 2012. Infants were followed until 6 months of age, and the outcome measure was inpatient admission for suspected pneumonia or diarrheal illness during the first 6 months of life. Risk factors were assessed using univariable logistic regression and multiple logistic regression. RESULTS: Of the 1049 infants seen at 6 months of age, 8.8 % required inpatient admission for suspected pneumonia and 4 % of infants required inpatient admission for diarrheal illness. One third of infants (32.8 %) were exclusively breast fed at 6 weeks of age. Exclusive breast feeding at 6 weeks of age significantly reduced the odds of inpatient admission for suspected pneumonia (Odds Ratio (OR) 0.39, 95 % Confidence Interval (CI) 0.20 to 0.75) and diarrheal illness (OR 0.37, 95 % CI 0.15 to 0.88). CONCLUSIONS: Exclusive breast feeding in early infancy reduces the risk of severe illness from diarrhea and suspected pneumonia. Public health programs to reduce the burden of inpatient admission from diarrheal and respiratory illness in rural Vietnam should address barriers to exclusive breast feeding.

Engineering of a lipid-polymer nanoarchitectural platform for highly effective combination therapy of doxorubicin and irinotecan.

We developed a highly stable lipid-polymer nanoarchitectural platform for effective combination therapy of doxorubicin and irinotecan in the polyelectrolyte complex nanoparticle core, followed by incorporation of the whole assembly into a lecithin bilayer. It shows great potential for the treatment of a broad range of cancers.

Volatile constituents of Amomum maximum Roxb and Amomum microcarpum C. F. Liang & D. Fang: two Zingiberaceae grown in Vietnam.

The chemical composition of essential oils obtained from the hydrodistillation of different parts of Amomum maximum Roxb and Amomum muricarpum C. F. Liang & D. Fang (Zingiberaceae) grown in Vietnam are reported. The analysis was performed by means of gas chromatography-flame ionisation detectoorand gas chromatography coupled with mass spectrometry. The major compounds identified in the oils of A. maximum were ß-pinene (20.4-40.8%), α-pinene (6.8-15.0%), ß-elemene (2.5-12.8%) and ß-caryophyllene (2.3-10.3%). Moreover, ß-phellandrene (11.6%) was present in the root oil. The main compound identified in all the oil samples of A. muricarpum was α-pinene (24.1-54.7%) and ß-pinene (9.2-25.9%). In addition, limonene (7.4%) and δ-3-carene (9.4%) were present in the leaves and stem oils, respectively. However, while ß-phellandrene (8.3%) could be seen prominent in the root oil, the fruits contained significant amount of zingiberene (6.3%). The largest amount of τ-muurolol (13.0%) was found in the flower oil.

Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study.

OBJECTIVE: To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. STUDY DESIGN: Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. RESULTS: Mean length-for-age z score was -0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m(2); 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (-41.5 g per twofold increase in ferritin; 95% CI -78 to -5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of -0.06 per 20 nmol/L; 95% CI -0.11 to -0.01) was observed. CONCLUSIONS: Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency.

A Brief History of Qinghaosu.

The 2015 Nobel Prize for Medicine or Physiology was awarded to William C. Campbell and Satoshi Omura for their discovery of avermectins, and to Tu You You for her contribution to the discovery of artemisinin. The discovery and development of qinghaosu (artemisinin) as an antimalarial drug is a remarkable and convoluted tale.

Postnatal growth outcomes and influence of maternal gestational weight gain: a prospective cohort study in rural Vietnam.

BACKGROUND: Suboptimal weight gain during pregnancy may result in adverse outcomes for both the mother and child, including increased risk of pre-eclampsia and gestational diabetes, delivery of low birth weight and small-for-gestational age (SGA) infants, and preterm delivery. The objectives of this study were to identify maternal predictors of rate of weight gain in pregnancy, and to evaluate the association of gestational weight gain with infant postnatal growth outcomes. METHODS: We conducted a prospective cohort study of infants born to women who had previously participated in a double-blind cluster randomized controlled trial of antenatal micronutrient supplementation, in Ha Nam province, Vietnam. Pregnant women (n = 1258) were seen at enrolment and 32 weeks gestation, and infants (n = 965) were followed until 6 months of age. Primary outcome was infant anthropometric indicators at 6 months of age (weight for age, length for age, weight for height z scores), and infant weight gain velocity during the first 6 months of life. RESULTS: Low body mass index (<18.5 kg/m2) was present in 26% of women, and rate of gestational weight gain was 0.4 kg per week [SD 0.12]. Rate of weight gain during pregnancy was significantly associated with infant weight-for-age (MD 1.13, 95% CI 0.58 to 1.68), length-for-age (MD 1.11, 95% CI 0.66 to 1.55), weight-for-length z scores (MD 0.63, 95% CI 0.07 to 1.19), and infant weight gain velocity during the first 6 months of life (MD 93.6 g per month, 95% CI 8.2 to 179.0). CONCLUSIONS: Rate of gestational weight gain is predictive of postnatal growth at six months of age in this setting. Public health programs should be targeted towards improving body mass index and weight gain in pregnant women in rural Vietnam.

Maternal vitamin D status and infant outcomes in rural Vietnam: a prospective cohort study.

OBJECTIVE: Vitamin D deficiency affects 1 billion people globally. It has an important role in bone homeostasis, brain development and modulation of the immune system and yet the impact of antenatal vitamin D deficiency on infant outcomes is poorly understood. We assessed the association of 25- hydroxyvitamin D levels (25-OHD) in late pregnancy and early infant growth and developmental outcomes in rural Vietnam. DESIGN AND METHODS: A prospective cohort study of 960 women who had previously participated in a double-blind cluster randomized controlled trial of antenatal micronutrient supplementation in rural Vietnam was undertaken. Maternal 25-OHD concentration was measured at 32 weeks gestation, and infants were followed until 6 months of age. Main outcome measures were cognitive, motor, socio-emotional and language scores using the Bayley Scales of Infant Development, 3rd edition, and infant length-for-age z scores at 6 months of age. RESULTS: 60% (582/960) of women had 25-OHD levels <75 nmol/L at 32 weeks gestation. Infants born to women with 25-OHD deficiency (<37.5 nmol/L) had reduced developmental language scores compared to those born to women who were vitamin D replete (≥75 nmol/L) (Mean Difference (MD) -3.48, 95% Confidence Interval (CI) -5.67 to -1.28). For every 25 nmol increase in 25-OHD concentration in late pregnancy, infant length-for-age z scores at 6 months of age decreased by 0.08 (95% CI -0.15 to -0.02). CONCLUSIONS: Low maternal 25- hydroxyvitamin D levels during late pregnancy are of concern in rural Vietnam, and are associated with reduced language developmental outcomes at 6 months of age. Our findings strengthen the evidence for giving vitamin D supplementation during pregnancy.

The effect of intermittent antenatal iron supplementation on maternal and infant outcomes in rural Viet Nam: a cluster randomised trial.

BACKGROUND: Anemia affects over 500 million women, and in pregnancy is associated with impaired maternal and infant outcomes. Intermittent antenatal iron supplementation is an attractive alternative to daily dosing; however, the impact of this strategy on infant outcomes remains unclear. We compared the effect of intermittent antenatal iron supplementation with daily iron supplementation on maternal and infant outcomes in rural Viet Nam. METHODS AND FINDINGS: This cluster randomised trial was conducted in Ha Nam province, Viet Nam. 1,258 pregnant women (< 16 wk gestation) in 104 communes were assigned to daily iron-folic acid (IFA), twice weekly IFA, or twice weekly multiple micronutrient (MMN) supplementation. Primary outcome was birth weight. Mean birth weight was 3,148 g (standard deviation 416). There was no difference in the birth weights of infants of women receiving twice weekly IFA compared to daily IFA (mean difference [MD] 28 g; 95% CI -22 to 78), or twice weekly MMN compared to daily IFA (MD -36.8 g; 95% CI -82 to 8.2). At 32 wk gestation, maternal ferritin was lower in women receiving twice weekly IFA compared to daily IFA (geometric mean ratio 0.73; 95% CI 0.67 to 0.80), and in women receiving twice weekly MMN compared to daily IFA (geometric mean ratio 0.62; 95% CI 0.57 to 0.68), but there was no difference in hemoglobin levels. Infants of mothers who received twice weekly IFA had higher cognitive scores at 6 mo of age compared to those who received daily IFA (MD 1.89; 95% CI 0.23 to 3.56). CONCLUSIONS: Twice weekly antenatal IFA or MMN did not produce a clinically important difference in birth weight, when compared to daily IFA supplementation. The significant improvement in infant cognitive outcomes at 6 mo of age following twice weekly antenatal IFA requires further exploration, and provides additional support for the use of intermittent, rather than daily, antenatal IFA in populations with low rates of iron deficiency. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry 12610000944033.

The potential role for acupuncture in treating symptoms in patients with lung cancer: an observational longitudinal study.

BACKGROUND: Most lung cancer patients experience multiple symptoms related either to the disease or its treatment. The commonly reported symptoms are pain, depression, anxiety, nausea, and poor well-being. The aim of the present study was to evaluate the effect of acupuncture as a potential treatment modality in symptomatic lung cancer patients. METHODS: This prospective observational study enrolled 33 lung cancer patients from the Peter Brojde Lung Cancer Centre between August 2010 and May 2012. All patients received 45-minute sessions of acupuncture, 1-2 times weekly for a minimum of 4 sessions. Symptom severity was assessed using the Edmonton Symptom Assessment System (esas) before and after completion of acupuncture. RESULTS: The study cohort included 30 patients with non-small- cell lung cancer and 3 with small-cell lung cancer. Mean age was 62 years (range: 36-88 years); 17 of the patients were women. Most of the patients had advanced-stage cancer (73%) and good performance status (Eastern Cooperative Oncology Group 0-1: 88%). Of these patients, 67% received anticancer treatment (chemotherapy or radiotherapy, or both) with acupuncture. Of the remaining 10 patients, 8 received acupuncture after a complete surgical resection of their tumour, and because of their advanced age, 2 received acupuncture and best supportive care. The median number of acupuncture sessions was 7 (interquartile range: 4-13 sessions). Statistically significant improvements in pain, appetite, nausea, nervousness, and well-being were observed. A clinically important improvement (2 points on the esas) was reported by 61% of patients for pain and by 33% for well-being. A significant positive correlation between improved well-being and the number of acupuncture sessions was observed. This correlation remained significant even after controlling for treatment and narcotic use. Receiver operating characteristic analysis demonstrated that a minimum of 6 acupuncture sessions are required for a 70% chance of a clinically important improvement in well-being. CONCLUSIONS: The present study is the first to demonstrate that acupuncture may be an effective approach for improving symptoms-in particular, pain and well-being-in lung cancer patients. Acupuncture is a safe and minimally invasive procedure, and it is potentially useful even in patients undergoing anticancer treatment.

Effects of infection control measures on acquisition of five antimicrobial drug-resistant microorganisms in a tetanus intensive care unit in Vietnam.

PURPOSE: To quantify the effects of barrier precautions and antibiotic mixing on prevalence and acquisition of five drug-resistant microorganisms within a single tetanus intensive care unit at a tertiary referral hospital in Ho Chi Minh City, Vietnam. METHODS: All patients admitted within the study period were included. After a 1-year baseline period, barrier precautions were implemented and the single empirical treatment ceftazidime was changed to mixing (per consecutive patient) of three different regimens (ceftazidime, ciprofloxacin, piperacillin-tazobactam). Markov chain modeling and genotyping were used to determine the effects of interventions on prevalence levels and the relative importance of cross-transmission and antibiotic-associated selection. RESULTS: A total of 190 patients were included in year 1 (2,708 patient days, 17,260 cultures) and 167 patients in year 2 (3,384 patient days, 20,580 cultures). In year 1, average daily prevalence rates for methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (excluding Klebsiella pneumoniae), Pseudomonas aeruginosa, gentamicin-resistant K. pneumoniae, and amikacin-resistant Acinetobacter species were 34.0, 61.3, 53.4, 65.7 and 57.1 %. After intervention, ceftazidime usage decreased by 53 %; the use of piperacillin-tazobactam and ciprofloxacin increased 7.2-fold and 4.5-fold, respectively. Adherence to hand hygiene after patient contact was 54 %. These measures were associated with a reduction of MRSA prevalence by 69.8 % (to 10.3 %), mainly because of less cross-transmission (88 % reduction), and of ESBL-producing Enterobacteriaceae prevalence by 10.3 % (non-significantly). In contrast, prevalence levels of the other three pathogens remained unaffected. CONCLUSION: The combination of simple infection control measures and antibiotic mixing was highly effective in reducing the prevalence of MRSA, but not of Gram-negative microorganisms.

Expression of cyclin D1a and D1b as predictive factors for treatment response in colorectal cancer.

BACKGROUND: The aim of this study was to investigate the value of the cyclin D1 isoforms D1a and D1b as prognostic factors and their relevance as predictors of response to adjuvant chemotherapy with 5-fluorouracil and levamisole (5-FU/LEV) in colorectal cancer (CRC). METHODS: Protein expression of nuclear cyclin D1a and D1b was assessed by immunohistochemistry in 335 CRC patients treated with surgery alone or with adjuvant therapy using 5-FU/LEV. The prognostic and predictive value of these two molecular markers and clinicopathological factors were evaluated statistically in univariate and multivariate survival analyses. RESULTS: Neither cyclin D1a nor D1b showed any prognostic value in CRC or colon cancer patients. However, high cyclin D1a predicted benefit from adjuvant therapy measured in 5-year relapse-free survival (RFS) and CRC-specific survival (CSS) compared to surgery alone in colon cancer (P=0.012 and P=0.038, respectively) and especially in colon cancer stage III patients (P=0.005 and P=0.019, respectively) in univariate analyses. An interaction between treatment group and cyclin D1a could be shown for RFS (P=0.004) and CSS (P=0.025) in multivariate analysis. CONCLUSION: Our study identifies high cyclin D1a protein expression as a positive predictive factor for the benefit of adjuvant 5-FU/LEV treatment in colon cancer, particularly in stage III colon cancer.

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions.

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or ß-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

Does a novel prefilled injection device make postpartum oxytocin easier to administer? Results from midwives in Vietnam.

OBJECTIVE: to assess the acceptability of the Uniject prefilled injection device for delivery of oxytocin in the third stage of labour, and the effect of the device on overall willingness to perform active management of the third stage of labour (AMTSL). DESIGN: descriptive study that used baseline and post-intervention questionnaires. SETTING: three districts in northern Vietnam. The study population consisted of 52 midwives from two districts where AMTSL was already practiced, and 35 midwives from a district where AMTSL was introduced as part of the study. MEASUREMENTS AND FINDINGS: the majority of midwives reported that the Uniject device was easier to use and preferable compared with ampoules and standard syringes. They found the training materials easy to understand. KEY CONCLUSIONS: the use of a prefilled injection device overcame many of the barriers cited by midwives with regard to the use of oxytocin in ampoules, such as trying to break ampoules and fill syringes in a hurry. This device enabled midwives to deliver the correct dose of oxytocin in the third stage of labour in a safe and timely way, while attending to the other needs of the mother and her newborn baby. IMPLICATIONS FOR PRACTICE: use of a prefilled injection device for oxytocin may increase the acceptability and practice of AMTSL in primary level facilities, thus reducing maternal mortality due to postpartum haemorrhage.