Colitis reduces active social engagement in mice and is ameliorated by supplementation with human microbiota members.

Multiple neurological disorders are associated with gastrointestinal (GI) symptoms, including autism spectrum disorder (ASD). However, it is unclear whether GI distress itself can modify aspects of behavior. Here, we show that mice that experience repeated colitis have impaired active social engagement, as measured by interactions with a foreign mouse, even though signs of colitis were no longer present. We then tested the hypothesis that individuals with ASD harbor a microbiota that might differentially influence GI health by performing microbiota transplantation studies into male germfree animals, followed by induction of colitis. Animals that harbor a microbiota from ASD individuals have worsened gut phenotypes when compared to animals colonized with microbiotas from familial neurotypical (NT) controls. We identify the enrichment of Blautia species in all familial NT controls and observe an association between elevated abundance of Bacteroides uniformis and reductions in intestinal injury. Oral treatment with either of these microbes reduces colon injury in mice. Finally, provision of a Blautia isolate from a NT control ameliorates gut injury-associated active social engagement in mice. Collectively, our data demonstrate that past intestinal distress is associated with changes in active social behavior in mice that can be ameliorated by supplementation of members of the human microbiota.

Process and Outcome Evaluation of a Mindfulness-Based Cognitive Therapy Intervention for Cisgender and Transgender African American Women Living with HIV/AIDS.

There is a need for evidence-based contextualized mental health interventions for persons living with HIV/AIDS. In the current study, the primary researcher conducted open trials with African American women living with HIV/AIDS (AAWLWHA) to examine the acceptability and feasibility of Project UPLIFT, a mindfulness-based cognitive therapy intervention that has demonstrated effectiveness in persons living with epilepsy. Women were recruited for a tele-delivered phone intervention group separated by gender identity, as well as participated in pre- and post-test assessments. Additionally, data on acceptability was collected. Both cis- and transgender women were highly satisfied with the intervention and demonstrated improvement in depressive and stress symptoms. The intervention seemed to be particularly feasible for cisgender women, though more qualitative mental health research may be warranted with transgender women. The current research has implications for the utility of mindfulness-based interventions such as UPLIFT, with AAWLWHA.

High dose Nitrate ingestion does not improve 40 km cycling time trial performance in trained cyclists.

This study evaluated the chronic effects of nitrate (NO3-) ingestion over three days, on 40 km TT performance in 11trained cyclists (VO2max: 60.8 ± 7.4 ml.kg-1.min-1; age: 36 ± 9 years; height: 1.80 ± 0.06 m; body mass: 87.2 ± 12.0 kg). Utilising a double-blind randomised cross-over design, participants completed three 40 km TT on a Velotron® ergometer following the ingestion of either a 140 ml of "BEET It sport®" NO3- shot containing 12.8 mmol or 800 mg of NO3-, a placebo drink or nothing (control). Performance, oxygen consumption (VO2), blood bicarbonate (HCO3-), pH and lactate (BLa) and ratings of perceived exertion (RPE) were measured every 10 km throughout the TT. The present findings show that NO3- ingestion had no effect on TT performance (NO3-: 4098.0 ± 209.8 vs. Placebo: 4161.9 ± 263.3 s, p = 0.296, ES = 0.11), or VO2 (p = 0.253, ES = 0.13). Similarly, blood lactate and RPE were also unaffected by the experimental conditions (p = 0.522, ES = 0.06; p = 0.085, ES = 0.30) respectively. Therefore, these results suggest that a high dose of NO3- over three days has limited efficacy as an ergogenic aid for 40 km TT cycling performance in trained cyclists.

Predicting fruit and vegetable consumption in long-haul heavy goods vehicle drivers: Application of a multi-theory, dual-phase model and the contribution of past behaviour.

Fruit and vegetable intake is insufficient in industrialized nations and long-haul heavy goods vehicle (HGV) drivers are considered a particularly at-risk group. The aim of the current study was to test the effectiveness of a multi-theory, dual-phase model to predict fruit and vegetable consumption in Australian long-haul HGV drivers. A secondary aim was to examine the effect of past fruit and vegetable consumption on model paths. A prospective design with two waves of data collection spaced one week apart was adopted. Long-haul HGV drivers (N = 212) completed an initial survey containing theory-based measures of motivation (autonomous motivation, intention), social cognition (attitudes, subjective norms, perceived behavioural control), and volition (action planning, coping planning) for fruit and vegetable consumption. One week later, participants (n = 84) completed a self-report measure of fruit and vegetable intake over the previous week. A structural equation model revealed that autonomous motivation predicted intentions, mediated through attitudes and perceived behavioural control. It further revealed that perceived behavioural control, action planning, and intentions predicted fruit and vegetable intake, whereby the intention-behaviour relationship was moderated by coping planning. Inclusion of past behaviour attenuated the effects of these variables. The model identified the relative contribution of motivation, social cognition, and volitional components in predicting fruit and vegetable intake of HGV drivers. Consistent with previous research, inclusion of past fruit and vegetable consumption led to an attenuation of model effects, particularly the intention-behaviour relationship. Further investigation is needed to determine which elements of past behaviour exert most influence on future action.

Genetic correlations between wool traits and meat quality traits in Merino sheep.

Genetic correlations between 29 wool production and quality traits and 25 meat quality and nutritional value traits were estimated for Merino sheep from an Information Nucleus (IN). Genetic correlations among the meat quality and nutritional value traits are also reported. The IN comprised 8 flocks linked genetically and managed across a range of sheep production environments in Australia. The wool traits included over 5,000 yearling and 3,700 adult records for fleece weight, fiber diameter, staple length, staple strength, fiber diameter variation, scoured wool color, and visual scores for breech and body wrinkle. The meat quality traits were measured on samples from the and included over 1,200 records from progeny of over 170 sires for intramuscular fat (IMF), shear force of meat aged for 5 d (SF5), 24 h postmortem pH (pHLL; also measured in the , pHST), fresh and retail meat color and meat nutritional value traits such as iron and zinc levels, and long-chain omega-3 and omega-6 polyunsaturated fatty acid levels. Estimated heritabilities for IMF, SF5, pHLL, pHST, retail meat color lightness (), myoglobin, iron, zinc and across the range of long-chain fatty acids were 0.58 ± 0.11, 0.10 ± 0.09, 0.15 ± 0.07, 0.20 ± 0.10, 0.59 ± 0.15, 0.31 ± 0.09, 0.20 ± 0.09, 0.11 ± 0.09, and range of 0.00 (eicosapentaenoic, docosapentaenoic, and arachidonic acids) to 0.14 ± 0.07 (linoleic acid), respectively. The genetic correlations between the wool production and meat quality traits were low to negligible and indicate that wool breeding programs will have little or no effect on meat quality. There were moderately favorable genetic correlations between important yearling wool production traits and the omega-3 fatty acids that were reduced for corresponding adult wool production traits, but these correlations are unlikely to be important in wool/meat breeding programs because they have high SE, and the omega-3 traits have little or no genetic variance. Significant genetic correlations among the meat quality traits included IMF with SF5 (-0.76 ± 0.24), fresh meat color * (0.50 ± 0.18), and zinc (0.41 ± 0.19). Selection to increase IMF will improve meat tenderness and color which may address some of the issues with Merino meat quality. These estimated parameters allow Merino breeders to combine wool and meat objectives without compromising meat quality.

Target-directed discovery and production of pharmaceuticals in transgenic mutant plant cells.

Plants are a source of complex bioactive compounds, with value as pharmaceuticals, or leads for synthetic modification. Many of these secondary metabolites have evolved as defenses against competing organisms and their pharmaceutical value is "accidental", resulting from homology between target proteins in these competitors, and human molecular therapeutic targets. Here we show that it is possible to use mutation and selection of plant cells to re-direct their "evolution" toward metabolites that interact with the therapeutic target proteins themselves. This is achieved by expressing the human target protein in plant cells, and selecting mutants for survival based on the interaction of their metabolome with this target. This report describes the successful evolution of hairy root cultures of a Lobelia species toward increased biosynthesis of metabolites that inhibit the human dopamine transporter protein. Many of the resulting selected mutants are overproducing the active metabolite found in the wild-type plant, but others overproduce active metabolites that are not readily detectable in non-mutants. This technology can access the whole genomic capability of a plant species to biosynthesize metabolites with a specific target. It has potential value as a novel platform for plant drug discovery and production, or as a means of optimizing the therapeutic value of medicinal plant extracts.

Sensitivity of the cochlear nerve to acoustic and electrical stimulation months after a vestibular labyrinthectomy in guinea pigs.

Single-sided deafness patients are now being considered candidates to receive a cochlear implant. With this, many people who have undergone a unilateral vestibular labyrinthectomy for the treatment of chronic vertigo are now being considered for cochlear implantation. There is still some concern regarding the potential efficacy of cochlear implants in these patients, where factors such as cochlear fibrosis or nerve degeneration following unilateral vestibular labyrinthectomy may preclude their use. Here, we have performed a unilateral vestibular labyrinthectomy in normally hearing guinea pigs, and allowed them to recover for either 6 weeks, or 10 months, before assessing morphological and functional changes related to cochlear implantation. Light sheet fluorescence microscopy was used to assess gross morphology throughout the entire ear. Whole nerve responses to acoustic, vibrational, or electrical stimuli were used as functional measures. Mild cellular infiltration was observed at 6 weeks, and to a lesser extent at 10 months after labyrinthectomy. Following labyrinthectomy, cochlear sensitivity to high-frequency acoustic tone-bursts was reduced by 16 ± 4 dB, vestibular sensitivity was almost entirely abolished, and electrical sensitivity was only mildly reduced. These results support recent clinical findings that patients who have received a vestibular labyrinthectomy may still benefit from a cochlear implant.

Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs.

Sleep disruption in tetraplegia: a randomised, double-blind, placebo-controlled crossover trial of 3 mg melatonin.

STUDY DESIGN: Randomised, double-blind, placebo-controlled crossover trial of melatonin supplementation to people with complete tetraplegia. OBJECTIVES: To investigate the effect that 3 mg melatonin supplementation has on objective and subjective sleep, quality of life and mood of people living with complete tetraplegia. SETTING: Austin Hospital Sleep Laboratory and participants' homes, Melbourne, Victoria, Australia. METHODS: Two week run-in followed by 3 week nightly administration of 3 mg melatonin or placebo, 2-week washout and further 3 week administration of the opposite treatment. Four testing sessions were conducted; the last nights of the run-in, treatment and washout periods. Testing sessions involved recording full polysomnography, completing a questionnaire battery and collecting urine and blood samples. The questionnaires assessed mood, sleep symptoms and health-related quality of life, and the urine and plasma samples assayed 6-sulphatoxymelatonin (aMT6s) and melatonin levels, respectively. A sleep diary was completed throughout the study. RESULTS: Eight participants (mean (s.d.): age 49.5 years (16), postinjury 16.9 years (7.1)) were recruited in which seven concluded the protocol. Endogenous-circulating melatonin was significantly higher (P < or = 0.01) following melatonin (urine: 152.94 µg h(-1) (74.51), plasma: 43,554.57 pM (33,527.11)) than placebo (urine: 0.86 µg h(-1) (0.40), plasma: 152.06 pM (190.55)). Subjective sleep improved significantly following melatonin specifically for duration of sleep per night and psychological wellbeing. Objective sleep showed a significant increase in light sleep with melatonin, with all other sleep parameters being unchanged. CONCLUSION: These results suggest that increasing melatonin in people with complete tetraplegia is beneficial, especially for subjective sleep. Investigation of the pharmacokinetics of melatonin metabolism in this population is warranted. SPONSORSHIP: This project is proudly supported by the Transport Accident Commission.

Skeletal effects of zoledronic acid in an animal model of chronic kidney disease.

UNLABELLED: Bisphosphonates reduce skeletal loss and fracture risk, but their use has been limited in patients with chronic kidney disease. This study shows skeletal benefits of zoledronic acid in an animal model of chronic kidney disease. INTRODUCTION: Bisphosphonates are routinely used to reduce fractures but limited data exists concerning their efficacy in non-dialysis chronic kidney disease. The goal of this study was to test the hypothesis that zoledronic acid produces similar skeletal effects in normal animals and those with kidney disease. METHODS: At 25 weeks of age, normal rats were treated with a single dose of saline vehicle or 100 µg/kg of zoledronic acid while animals with kidney disease (approximately 30% of normal kidney function) were treated with vehicle, low dose (20 µg/kg), or high dose (100 µg/kg) zoledronic acid, or calcium gluconate (3% in the drinking water). Skeletal properties were assessed 5 weeks later using micro-computed tomography, dynamic histomorphometry, and mechanical testing. RESULTS: Animals with kidney disease had significantly higher trabecular bone remodeling compared to normal animals. Zoledronic acid significantly suppressed remodeling in both normal and diseased animals yet the remodeling response to zoledronic acid was no different in normal and animals with kidney disease. Animals with kidney disease had significantly lower cortical bone biomechanical properties; these were partially normalized by treatment. CONCLUSIONS: Based on these results, we conclude that zoledronic acid produces similar amounts of remodeling suppression in animals with high turnover kidney disease as it does in normal animals, and has positive effects on select biomechanical properties that are similar in normal animals and those with chronic kidney disease.

Effect of surface treatments on microtensile bond strength of repaired aged silorane resin composite.

OBJECTIVE: This laboratory study compared the repaired microtensile bond strengths of aged silorane resin composite using different surface treatments and either silorane or methacrylate resin composite. METHODS: One hundred eight silorane resin composite blocks (Filtek LS) were fabricated and aged by thermocycling between 8°C and 48°C (5000 cycles). A control (solid resin composite) and four surface treatment groups (no treatment, acid treatment, aluminum oxide sandblasting, and diamond bur abrasion) were tested (N=12 blocks, 108 beams/group). Each treatment group was randomly divided in half and repaired with either silorane resin composite (LS adhesive) or methacrylate resin composite (Filtek Z250/Single Bond Plus). After 24 hours in 37°C distilled water, microtensile bond strength testing was performed using a non-trimming technique. Surface topography after surface treatment was analyzed using scanning electron microscopy (SEM). Failure mode was examined using optical microscopy (50×). RESULTS: Weibull-distribution survival analysis revealed that aluminum oxide sandblasting followed by silorane or methacrylate resin composite and acid treatment with methacrylate resin composite provided insignificant differences from the control (p>0.05). All other groups were significantly lower than the control. Failure was primarily adhesive in all groups. CONCLUSION: Aluminum oxide sandblasting produced microtensile bond strength not different from the cohesive strength of silorane resin composite. After aluminum oxide sandblasting, aged silorane resin composite can be repaired with either silorane resin composite with LS system adhesive or methacrylate resin composite with methacrylate dental adhesive.

The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers.

OBJECTIVE: To investigate if a lower dose of arginine in the form of an oral nutritional supplement can show similar benefit in the healing rate of pressure ulcers compared with the current evidence for 9g of arginine. METHOD: Twenty-three inpatients with category II, III or IV pressure ulcers were randomised to receive daily, for 3 weeks, the standard hospital diet plus 4.5 or 9g arginine in the form of a commercial supplement. Pressure ulcer size and severity was measured weekly (by PUSH tool; pressure ulcer scale for healing; 0= completely healed, 17= greatest severity). Nutritional status was determined by Subjective Global Assessment. RESULTS: There were no significant differences in patients' age, gender, BMI, haemoglobin levels, albumin levels and diagnosis of diabetes between treatment groups. There was a significant decrease in pressure ulcer severity over time (p < 0.001), with no evidence of a difference in healing rate between the two arginine dosages (p=0.991). Based on expected healing time, patients in both treatment groups were estimated to achieve an almost 2-fold improvement compared with the historical control group. Patients categorised as malnourished showed clinically significant impaired healing rates compared with well nourished patients (p=0.057), although this was unaffected by arginine dosage (p=0.727). CONCLUSION: Similar clinical benefits in healing of pressure ulcers can be achieved with a lower dosage of arginine, which can translate into improved concordance and significant cost-savings for both the health-care facilities and for patients.

Developing therapeutic microRNAs for cancer.

Despite substantial progress in understanding the cancer-signaling network, effective therapies remain scarce due to insufficient disruption of oncogenic pathways, drug resistance and drug-induced toxicity. This complexity of cancer defines an urgent goal for researchers and clinicians to develop novel therapeutic strategies. The discovery of microRNAs (miRNAs) provides new hope for accomplishing this task. Supported by solid evidence for a critical role in cancer and bolstered by a unique mechanism of action, miRNAs are likely to yield a new class of targeted therapeutics. In contrast to current cancer medicines, miRNA-based therapies function by subtle repression of gene expression on a yet large number of oncogenic factors and are, therefore, anticipated to be highly efficacious. After the completion of target validation for several candidates, the development of therapeutic miRNAs is now moving to a new stage that involves pharmacological drug delivery, preclinical toxicology and regulatory guidelines.

Effect of an arginine-containing nutritional supplement on pressure ulcer healing in community spinal patients.

OBJECTIVE: To determine whether or not the use of an arginine-containing nutritional supplement could result in significantly shorter pressure ulcer (PU) healing times in people with spinal cord injuries living in the community, compared with a comparative historical control group. METHOD: Eighteen spinal-cord-injured patients (all part of a hospital spinal outreach service) received 9 g of a commercial powdered arginine supplement per day until full PU healing occurred. Healing rates were compared against 17 historical control patients (as assessed by medical history audit). RESULTS: Baseline characteristics (age, gender, injury level and time) were similar between groups. Mean ulcer healing times were 10.5 +/- 1.3 weeks versus 21 +/- 3.7 weeks (p<0.05) in the intervention and control groups respectively. Comparison of healing rates in the intervention group against expected healing rates derived from the medical literature showed that intervention patients had a significantly shorter mean healing time (category 2 PU: 5.5+/-1.3 weeks versus 13.4 weeks; category 3 PU: 12.5 +/- 1.9 weeks versus 18.2 weeks; category 4 PU: 14.4 +/- 4.8 weeks versus 22.1 weeks). A diagnosis of diabetes did not significantly alter healing rates in either group. CONCLUSION: Results from this observational study show a promising benefit of arginine supplementation on PU healing for individuals with spinal cord injury living in the community.

Impact of short-course quinolone therapy on susceptible and resistant populations of Staphylococcus aureus.

We previously demonstrated that therapy duration has a differential impact on susceptible and resistant subpopulations of Staphylococcus aureus. What our previous investigation did not address was what would transpire after stopping therapy and whether these events would be different in susceptible and resistant subpopulations. We used the regimen previously demonstrated to amplify resistant subpopulation at day 4-5 (area under the concentration-time curve/minimum inhibitory concentration ratio, 100). Therapy was started in our hollow-fiber infection model on day 0; garenoxacin was administered in 4, 5, or 6 doses (days 3-5). The system was observed until day 13. Four drug doses kept the susceptible population dominant, but with the resistant subpopulation amplifying. Five and 6 doses caused the resistant population to exceed the susceptible population at the end of therapy and for a variable time thereafter. Ultimately, the susceptible population became dominant by day 13. Modeling demonstrated that the resistant isolates grew more slowly and had a higher natural death rate.

Impact of traditional medicinal plant extracts on antiretroviral drug absorption.

ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Traditional herbal medicines are often used for the treatment of different diseases in developing countries, especially in the rural areas where a lack of an efficient primary health care system is usually experienced. Many patients infected with the human immunodeficiency virus are taking traditional herbal medicines in conjunction with their modern antiretroviral medication and drug-herb interactions can occur in these cases. AIM OF THE STUDY: To investigate the effect of water extracts of two traditional medicinal plants, Hypoxis hemerocallidea and Sutherlandia frutescens as well as l-canavanine (a constituent of Sutherlandia frutescens) on the transport of nevirapine across human intestinal epithelial cells. MATERIALS AND METHODS: Nevirapine transport in the apical to basolateral and basolateral to apical directions across Caco-2 cell monolayers was determined alone (normal control) and in the presence of verapamil (positive control), water extracts of Hypoxis hemerocallidea and Sutherlandia frutescens and an aqueous solution of l-canavanine. The cumulative transport and apparent permeability coefficient (P(app)) values were calculated and compared. RESULTS: Nevirapine alone was substantially effluxed in the basolateral to apical direction across the intestinal epithelial cell monolayers, which was statistically significantly (p < or = 0.05) decreased by addition of verapamil, Hypoxis hemerocallidea extract and the l-canavinine solution. The effect of Sutherlandia frutescens on nevirapine transport was not statistically significantly different from the control. CONCLUSIONS: Hypoxis hemerocallidea and l-canavanine interact with the efflux of nevirapine across intestinal epithelial cells and therefore can potentially increase the bioavailability of this antiretroviral drug when taken concomitantly.

Effect of a Bacillus-based direct-fed microbial feed supplement on growth performance and pen cleaning characteristics of growing-finishing pigs.

A direct-fed microbial (DFM) based on a combination of Bacillus organisms specifically selected to increase the manure decomposition process was evaluated to determine its efficacy for improving growth performance and manure dissolution time. Three experiments involving 336 crossbred barrows and gilts were conducted to determine the effect of the Bacillus-based direct-fed microbial on growth performance and pen cleaning time. In each experiment, 2 dietary treatments (0 and 0.05% DFM) were fed during the growing-finishing period throughout the experiment, such that the DFM provided 1.47 x 10(8) cfu of Bacillus organisms per gram of supplement. Data from the 3 experiments were combined for analysis, such that there were 28 pens representing each of the 2 treatments. Pigs were weighed and feed intake was determined at the initiation and termination of each phase (starter, grower, and finisher). At the end of Exp. 1 and 3, pen cleaning time was determined by measuring the time required for each pen to be scraped and washed with a high-pressure sprayer. Additionally, 2 solid manure mat samples weighing approximately 4 g each were collected from solid manure buildup in each pen (16 pens/treatment), and the time required to completely disperse each manure mat sample was determined. Gain:feed improved (P < 0.05) in pigs fed Bacillus compared with the control diet during the finisher phase and throughout the combined growing-finishing period. The time required to dissolve the manure mat was reduced (P < 0.01) in samples collected from pens containing pigs fed Bacillus compared with samples from control pens. An additional evaluation was conducted in a commercial swine production facility using statistical process control analysis. Statistical process control analysis determined that supplementation with Bacillus increased the expected mean for ADG and decreased the expected mean for death loss percentage. Supplementation with a DFM composed of specifically selected Bacillus organisms improved G:F and decreased the time required to disperse a swine manure mat sample in a controlled study conducted at swine research facilities. Furthermore, when evaluated in a commercial swine production facility, the Bacillus-based DFM improved ADG and reduced mortality of pigs during the growing-finishing period.

Infant morbidity in an Indian slum birth cohort.

OBJECTIVE: To establish incidence rates, clinic referrals, hospitalisations, mortality rates and baseline determinants of morbidity among infants in an Indian slum. DESIGN: A community-based birth cohort with twice-weekly surveillance. SETTING: Vellore, South India. SUBJECTS: 452 newborns recruited over 18 months, followed through infancy. MAIN OUTCOME MEASURES: Incidence rates of gastrointestinal illness, respiratory illness, undifferentiated fever, other infections and non-infectious morbidity; rates of community-based diagnoses, clinic visits and hospitalisation; and rate ratios of baseline factors for morbidity. RESULTS: Infants experienced 12 episodes (95% confidence interval (CI) 11 to 13) of illness, spending about one fifth of their infancy with an illness. Respiratory and gastrointestinal symptoms were most common with incidence rates (95% CI) of 7.4 (6.9 to 7.9) and 3.6 (3.3 to 3.9) episodes per child-year. Factors independently associated with a higher incidence of respiratory and gastrointestinal illness were age (3-5 months), male sex, cold/wet season and household involved in beedi work. The rate (95% CI) of hospitalisation, mainly for respiratory and gastrointestinal illness, was 0.28 (0.22 to 0.35) per child-year. CONCLUSIONS: The morbidity burden due to respiratory and gastrointestinal illness is high in a South Indian urban slum, with children ill for approximately one fifth of infancy, mainly with respiratory and gastrointestinal illnesses. The risk factors identified were younger age, male sex, cold/wet season and household involvement in beedi work.

Veterinary aspects and perspectives of nutrigenomics: a critical review.

Nutrigenomics examines nutrient-gene interactions on a genome-wide scale. Increased dietary fat or higher non-esterified fatty acids (NEFA) from starvation-induced mobilisation may enhance hepatic oxidation and decrease esterification of fatty acids by reducing the expression of the fatty acid synthase gene. The key factors are the peroxisome proliferator-activated receptors (PPARs). Dietary carbohydrates--both independently and through insulin effect--influence the transcription of the fatty acid synthase gene. Oleic acid or n-3 fatty acids downregulate the expression of leptin, fatty acid synthase and lipoprotein lipase in retroperitoneal adipose tissue. Protein-rich diets entail a shortage of mRNA necessary for expression of the fatty acid synthase gene in the adipocytes. Conjugated linoleic acids (CLAs) are activators of PPAR and also induce apoptosis in adipocytes. Altered rumen microflora produces CLAs that are efficient inhibitors of milk fat synthesis in the mammary gland ('biohydrogenation theory'). Oral zinc or cadmium application enhances transcription rate in the metallothionein gene. Supplemental CLA in pig diets was found to decrease feed intake and body fat by activating PPARgamma-responsive genes in the adipose tissue. To prevent obesity and type II diabetes, the direct modulation of gene expression by nutrients is also possible. Nutrigenomics may help in the early diagnosis of genetically determined metabolic disorders and in designing individualised diets for companion animals.

Impact of drug-exposure intensity and duration of therapy on the emergence of Staphylococcus aureus resistance to a quinolone antimicrobial.

We have shown previously in animal model and in vitro systems that antimicrobial therapy intensity has a profound influence on subpopulations of resistant organisms. Little attention has been paid to the effect of therapy duration on resistant subpopulations. We examined the influence of therapy intensity (area under the concentration/time curve for 24 h:minimum inhibitory concentration [AUC24:MIC] ratio) and therapy duration on resistance emergence using an in vitro model of Staphylococcus aureus infection. AUC24:MIC ratios of>or=100 were necessary to kill a substantial portion of the total population. Importantly, we demonstrated that therapy duration is a critical parameter. As the duration increased beyond 5 days, the intensity needed to suppress the antibiotic-resistant subpopulations increased, even when the initial bacterial kill was>4 log10 (cfu/mL). These findings were prospectively validated in an independent experiment in which exposures were calculated from the results of fitting a large mathematical model to all data simultaneously. All of the prospectively determined predictions were fulfilled in this validation experiment.