Evaluation of Long-Term Nutrition Outcomes After Duodenal Switch: A Systematic Review and Meta-Analysis.

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective and durable metabolic and bariatric surgery to achieve a target weight loss. However, many surgeons are hesitant to adopt BPD-DS due to a lack of training, technical complexity, and long-term nutrition deficiencies. This meta-analysis aimed to investigate long-term nutrition outcomes after primary BPD-DS in the management of obesity. METHODS: Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles from their inception to February 2023 by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42023391316). RESULTS: From 834 studies screened, 8 studies met the eligibility criteria, with a total of 3443 patients with obesity undergoing primary BPD-DS. At long-term follow-up (≥5 years), 25.4% of patients had vitamin A deficiency (95% CI: -.012, .520, I2 = 94%), and 57.3% had vitamin D deficiency (95% CI: .059, 1.086, I2 = 86%). Calcium deficiency was observed in 125 patients (22.2%, 95% CI: .061, .383, I2 = 97%), and 69.7% had an abnormal parathyroid hormone level (95% CI: .548, .847, I2 = 78%). Ferritin level was abnormal in 30 patients (29.0%, 95% CI: .099, .481, I2 = 79%). CONCLUSIONS: Despite displaying comparable nutrition-related outcomes to mid-term follow-up, our study demonstrated that BPD-DS could result in a high level of long-term nutrition deficiency after BPD-DS for selected patients. However, further randomized controlled studies with standardized supplementation regimens and improvement in compliance are necessary to evaluate and prevent long-term nutritional deficiencies after BPD-DS.

Quantification of zinc concentrations in serum, milk and faeces of dairy cattle as a measure of effective zinc supplementation for management of facial eczema.

AIMS: To investigate the relationship between Zn concentrations in serum and those in milk or faeces, and to assess the ability of the Zn concentrations in milk, serum and faeces to predict intake of ZnO in dairy cattle. METHOD: Seventy cows from one commercial farm in the Waikato region of New Zealand received one of seven dose rates (0, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 g/100 kg bodyweight (BW)) of ZnO given by oral drench, every morning, for 7 consecutive days. Every afternoon, milk and blood samples were collected from all cows. Free-catch faecal samples were collected during the afternoon milking on 3 days throughout the trial.Linear mixed models were used to assess the relationship between the concentration of Zn in serum and that in milk, and in faeces, respectively, and the relationship between dose rate of ZnO and concentrations of Zn in serum, faeces and milk, respectively. Receiver operating characteristic curve analysis was used to determine the ability of the Zn concentration in serum, milk and faeces to predict that a cow had been treated with a dose of ZnO ≥2.5 g/100 kg, the industry-recommended dose rate needed to protect against facial eczema. RESULTS: A 1-µmol/L increase in Zn concentration in milk was associated with a 0.14 (95% CI = 0.11-0.17) µmol/L increase in Zn concentration in serum. Zn concentration in faeces was scaled by its SD; a 1 SD increase was associated with a 1.83 (95% CI = 0.54-3.12) µmol/L increase in zinc concentration in serum. Zn concentrations in serum and faeces increased with increasing dose rates of ZnO. No differences in Zn concentrations in milk were noted between animals dosed with 1.5-3.5 g ZnO/100 kg BW, inclusive. At the optimal threshold of Zn concentration in serum to predict protective ZnO intake (22 µmol/L), the sensitivity was 0.76 (95% CI = 0.69-0.82) and specificity 0.85 (95% CI = 0.80-0.89). For the concentration of Zn in faeces, the optimal threshold was 17.36 mmol/kg, with a corresponding sensitivity of 0.84 (95% CI = 0.84-0.85) and specificity of 0.85 (95% CI = 0.73-0.94). At the optimal threshold for the Zn concentration in milk (76.6 µmol/L), the sensitivity was lower than the other two sample types at 0.59 (95% CI = 0.52-0.67), but with a similar specificity of 0.84 (95% CI = 0.79-0.88). CONCLUSIONS AND CLINICAL RELEVANCE: The concentration of Zn in milk shows promise as an initial screening test to identify dairy farms that do not provide adequate zinc to provide protection against FE.

An observational study on the relationship between zinc concentrations in bulk tank milk and in serum and farmer-reported zinc supplementation of dairy cattle for facial eczema prophylaxis.

AIMS: To describe the concentration of Zn in bulk tank milk (BTM) in a sample of New Zealand dairy farms, investigate the association between the method of Zn administration for facial eczema prophylaxis and Zn concentrations in BTM and investigate the relationship between the concentration of Zn in serum and that in BTM. METHODS: Multiple BTM samples (n = 3,330) collected during milk pick-up by the milk tanker driver were stored and tested for 121 farms, in Northland (n = 50), Waikato (n = 51) and Southland (n = 20) from February to May 2017. Enrolled farms provided retrospective information on the type of Zn supplementation (if any) used for the prevention of facial eczema and the timeframe over which supplementation occurred. In addition, the concentration of Zn in serum was measured in blood samples collected from ≥15 cattle per farm for 22 farms from Northland (n = 11) and Waikato (n = 11), and compared against the concentrations of Zn in BTM on the day of blood sampling. A linear mixed model was used to model log Zn concentrations in BTM using method of Zn supplementation, region, milk fat and protein percentage, volume of milk, and frequency of milk pick-up as risk factors. A mixed logistic regression model was used to assess the relationship between Zn concentrations in BTM and the presence of cows with a concentration of Zn in serum of ≥20 µmol/L. RESULTS: The median Zn concentration in BTM was 67.9 (min 38.9, max 146.6) µmol/L. The median range of Zn concentrations for repeated samples of BTM within farm was 22.6 µmol/L. In comparison to farms that did not use any form of Zn supplementation, farms that supplemented Zn through a slow-release capsule, oral drench, in feed or a combination of in-feed and water were associated with increased concentrations of Zn in BTM (p < 0.001). There was no difference in Zn concentrations in BTM between farms that administered Zn through the water only and farms that did not administer Zn (p = 0.22). Every 15.3 µmol/L increase in Zn concentration in BTM was associated with 2.2 times (95% CI=1.7-2.9) the odds of a cow having Zn concentration in serum ≥20 µmol/L. CONCLUSION AND CLINICAL RELEVANCE: Zn concentration in BTM is highly variable between farms, days and Zn administration method. Zn concentration in BTM content has modest potential as a way to signal whether a herd has achieved the high Zn status considered to be protective against FE.

Computed tomography imaging in ventral hernia repair: can we predict the need for myofascial release?

INTRODUCTION: Currently, the need for additional myofascial release (AMR) in addition to retromuscular dissection during open Rives-Stoppa hernia repair is determined intraoperatively based on the discretion of the surgeon. We developed a novel method to objectively predict the need for AMR preoperatively using computed tomography (CT)-measured rectus width to hernia width ratio (RDR). METHODS: A retrospective chart review of all patients who underwent open retro-muscular mesh repair of midline ventral hernia between August 1, 2007 and February 1, 2018, who had a preoperative CT scan within 1 year prior to their operation. The primary endpoint was the ability of the defect ratio to predict the need for AMR in pursuit of fascial closure. The secondary endpoint was the ability of Component Separation Index (CSI) to predict the need for AMR to obtain fascial closure. RESULTS: Of 342 patients, 208 repaired with rectus abdominis release alone (RM group), while 134 required AMR (RM + group). An RDR of > 1.34 on area under the curve analysis predicted the need for AMR with 77.6% accuracy. There was a linear decrease in the need for AMR with increasing RDR: RDR < 1 required AMR in 78.8% of cases, RDR 1.1-1.49 in 52%, RDR 1.5-1.99 in 32.1%, and RDR > 2 in just 10.8%. Similarly, CSI > 0.146 predicted the need for AMR with 76.3% accuracy on area under the curve analysis. CONCLUSION: The RDR is a practical and reliable tool to predict the ability to close the defect during open Rives-Stoppa ventral hernia repair without AMR. An RDR of > 2 portends fascial closure with rectus abdominis myofascial release alone in 90% of cases.

Australian women's understanding of menopause and its consequences: a qualitative study.

BACKGROUND: This study was undertaken to determine women's knowledge of menopause and its consequences, and their menopause-related health-care experiences. METHODS: Participants were recruited to this cross-sectional qualitative study from a nationally, representative sample of Australian women. Recruitment was stratified by age to achieve groups of premenopausal (PRE), perimenopausal (PERI), early postmenopausal (E-POST), and late postmenopausal (L-POST) women. RESULTS: The 32 participants were aged 46-69 years: 10 PRE, three PERI, 11 E-POST and eight L-POST women. All understood that menopause meant the end of reproductive function and were aware of menopause-associated symptoms. Most PRE and E-POST women referred to lifestyle changes to optimize health, and self-help and complementary therapies to manage symptoms. E-POST and L-POST women were more likely to nominate seeing a doctor for overall health and symptom management. Menopausal hormone therapy (MHT) was viewed negatively, with shared perceptions of cancer risk and over-prescription. A strong theme was lack of knowledge of long-term menopause sequelae, with only four women nominating osteoporosis. CONCLUSIONS: Our in-depth qualitative study would suggest that, while Australian midlife women have a good understanding of the immediate effects of menopause, their lack of knowledge of the long-term consequences is concerning. Despite the effectiveness and safety of MHT, the overall attitude to MHT remains negative.

Systematically Building a Model to Support and Unify Advanced Practice Providers.

Nursing leaders at the University of South Alabama (USA) Health collaborated to explore the need for a structured practice model for advanced practice providers (APP). The goal of this collaboration was to create an organizational structure where APPs could thrive clinically and professionally.

An investigation into heterogeneity in a single vein-type uranium ore deposit: Implications for nuclear forensics.

Minor element composition and rare earth element (REE) concentrations in nuclear materials are important as they are used within the field of nuclear forensics as an indicator of sample origin. However recent studies into uranium ores and uranium ore concentrates (UOCs) have shown significant elemental and isotopic heterogeneity from a single mine site such that some sites have shown higher variation within the mine site than that seen between multiple sites. The elemental composition of both uranium and gangue minerals within ore samples taken along a single mineral vein in South West England have been measured and reported here. The analysis of the samples was undertaken to determine the extent of the localised variation in key elements. Energy Dispersive X-ray spectroscopy (EDS) was used to analyse the gangue mineralogy and measure major element composition. Minor element composition and rare earth element (REE) concentrations were measured by Electron Probe Microanalysis (EPMA). The results confirm that a number of key elements, REE concentrations and patterns used for origin location do show significant variation within mine. Furthermore significant variation is also visible on a meter scale. In addition three separate uranium phases were identified within the vein which indicates multiple uranium mineralisation events. In light of these localised elemental variations it is recommended that representative sampling for an area is undertaken prior to establishing the REE pattern that may be used to identify the originating mine for an unknown ore sample and prior to investigating impact of ore processing on any arising REE patterns.

ICARUSS, the Integrated Care for the Reduction of Secondary Stroke trial: rationale and design of a randomized controlled trial of a multimodal intervention to prevent recurrent stroke in patients with a recent cerebrovascular event, ACTRN = 12611000264987.

BACKGROUND: The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. AIM: To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. DESIGN: A prospective, Australian, multicentre, randomized controlled trial. SETTING: Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. SUBJECTS: 1000 stroke survivors recruited as from March 2007 with a recent (<3 months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). RANDOMIZATION: Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). INTERVENTION: Exposure to the ICARUSS model of integrated care or usual care. PRIMARY OUTCOME: The composite of stroke, MI or death from any vascular cause, whichever occurs first. SECONDARY OUTCOMES: Risk factor management in the community, depression, quality of life, disability and dementia. STATISTICAL POWER: With 1000 patients followed up for a median of one-year, with a recurrence rate of 7-10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points CONCLUSION: The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level.

Fecal short-chain fatty acids of very-low-birth-weight preterm infants fed expressed breast milk or formula.

OBJECTIVES: In preterm infants, the metabolic responses of gastrointestinal (GI) bacteria to different diets are poorly understood despite the possible effects on GI health. Therefore, we tested the hypothesis that diet influences bacterial metabolism by measuring short-chain fatty acids (SCFAs) in stool samples from very-low-birth-weight (VLBW) preterm infants without GI disorder as surrogate biomarkers of bacterial metabolism. METHODS: Ion chromatography was used to measure fecal SCFAs (acetate, formate, propionate, butyrate, and isobutyrate), lactate, and chloride in fresh stool samples collected from 32 preterm infants (without major congenital anomalies, GI disorders, or a recent history of antibiotic administration and on full feed of either expressed maternal breast milk [EBM; n = 13] or a formula for preterm infants [Similac Special Care Formula; preterm formula, PTF; n = 19]). RESULTS: The mean birth weight was 972 g, the mean gestational age was 27 weeks, and the mean postnatal age at first stool sample was 36 days. When adjusted for gestational age, the stools of EBM infants had higher concentrations (micromoles per gram of stool) of total SCFA (128 vs 68; P = 0.002), acetate (41 vs 13; P = 0.005), propionate (15.1 vs 4.4; P = 0.003), and chloride (21,814 vs 10,652; P = 0.02). Interactions between postnatal age and diet were detected for lactate (P = 0.05), propionate (P = 0.03), and butyrate (P = 0.03). CONCLUSIONS: Diets fed to VLBW preterm infants influence fecal SCFA profiles, and hence the metabolism of the GI bacteria, and potentially the health of preterm infants. The responses of bacterial metabolism to diet are influenced with postnatal age and gestational age at birth.

Integrated care improves risk-factor modification after stroke: initial results of the Integrated Care for the Reduction of Secondary Stroke model.

OBJECTIVE: Despite evidence demonstrating that risk-factor management is effective in reducing recurrent cerebrovascular disease, there are very few structured care programmes for stroke survivors. The aim was to implement and evaluate an integrated care programme in stroke. METHODS: 186 patients with stroke were randomised to either the treatment (integrated care) or control (usual care) group and were followed up over 12 months. The Integrated Care for the Reduction of Secondary Stroke (ICARUSS) model of integrated care involved collaboration between a specialist stroke service, a hospital coordinator and a patient's general practitioner. The primary aim was to promote the management of vascular risk factors through ongoing patient contact and education. RESULTS: In the 12 months poststroke, systolic blood pressure (sBP) decreased in the treatment group but increased in controls. The group difference was significant, and remained so when age, sex, disability and sBP at discharge were accounted for (p = 0.04). Treatment patients also exhibited better modification of body mass index (p = 0.007) and number of walks taken (p<0.001) than controls. Rankin scores indicated significantly reduced disability in treatment patients relative to controls in the year poststroke (p = 0.003). CONCLUSIONS: Through an integrated system of education, advice and support to both patient and GP, the ICARUSS model was effective in modifying a variety of vascular risk factors and therefore should decrease the likelihood or recurrent stroke or vascular event.

Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis.

OBJECTIVE: The goal of this investigation was to demonstrate that internuclear ophthalmoparesis (INO) can be utilized to model the effects of body temperature-induced changes on the fidelity of axonal conduction in multiple sclerosis (Uhthoff's phenomenon). METHODS: Ocular motor function was measured using infrared oculography at 10-minute intervals in patients with multiple sclerosis (MS) with INO (MS-INO; n = 8), patients with MS without INO (MS-CON; n = 8), and matched healthy controls (CON; n = 8) at normothermic baseline, during whole-body heating (increase in core temperature 0.8 degrees C as measured by an ingestible temperature probe and transabdominal telemetry), and after whole-body cooling. The versional disconjugacy index (velocity-VDI), the ratio of abducting/adducting eye movements for velocity, was calculated to assess changes in interocular disconjugacy. The first pass amplitude (FPA), the position of the adducting eye when the abducting eye achieves a centrifugal fixation target, was also computed. RESULTS: Velocity-VDI and FPA in MS-INO patients was elevated (p < 0.001) following whole body heating with respect to baseline measures, confirming a compromise in axonal electrical impulse transmission properties. Velocity-VDI and FPA in MS-INO patients was then restored to baseline values following whole-body cooling, confirming the reversible and stereotyped nature of this characteristic feature of demyelination. CONCLUSIONS: We have developed a neurophysiologic model for objectively understanding temperature-related reversible changes in axonal conduction in multiple sclerosis. Our observations corroborate the hypothesis that changes in core body temperature (heating and cooling) are associated with stereotypic decay and restoration in axonal conduction mechanisms.

Broiler performance and carcass characteristics when fed diets containing lysine maize (LY038 or LY038 x MON 810), control, or conventional reference maize.

Lysine maize (Zea mays), LY038, was developed through the application of modern biotechnology to accumulate free Lys in the germ portion of maize grain and provide an alternative to direct addition of supplemental Lys to poultry diets. Maize LY038 x MON 810 was produced by conventional breeding of LY038 with MON 810, which provides the corn plant protection against feeding damage from the European corn borer. A 42-d broiler feeding study (10 pens of 10 male Cobb x Cobb 500 broilers/treatment) was conducted to compare the feeding value of grain from LY038 or LY038 x MON 810 to that of a conventional control (similar genetic background to the test maize) and 5 conventional maize hybrids. The LY038 and LY038 x MON 810 maize-based diets and control and conventional reference maize-based diets supplemented with l-Lys HCl were formulated to a Lys level below that required for optimal bird performance, whereas all other essential amino acids were present at levels, relative to Lys, above those required for optimal bird performance [1.05% and 0.90% total Lys (as-fed) for d 0 to 21 and d 21 to 42, respectively]. Total Lys level in control and reference maize-based diets without supplemental l-Lys HCl was formulated to be 0.079% lower than supplemented diets. Weight gain, feed efficiency, and carcass yield and composition of broilers fed diets containing LY038 or LY038 x MON 810 were not different (P > 0.05) from that of broilers fed l-Lys HCl-supplemented diets and were superior (P < or = 0.05) to that of broilers fed conventional maize diets without supplemental l-Lys HCl. Both broiler performance and carcass data demonstrate that the bioefficacy of the incremental Lys in LY038 or LY038 x MON 810 grain was not different from that of Lys in conventional maize diets supplemented with l-Lys HCl. Thus, LY038 and LY038 x MON 810 can be considered as wholesome as and more nutritious than conventional maize due to its higher-than-average Lys content.

Nasal administration of an angiotensin antagonist in the rat model: effect of bioadhesive formulations on the distribution of drugs to the systemic and central nervous systems.

The effect of bioadhesive formulations on the direct transport of an angiotensin antagonist drug ((14)C-GR138950) from the nasal cavity to the central nervous system was evaluated in a rat model. Three different bioadhesive polymer formulations (3% pectin LM-5, 1.0% pectin LM-12 and 0.5% chitosan G210) containing the drug were administered nasally to rats by inserting a dosing cannula 7mm into the nasal cavity after which the plasma and brain tissue levels were measured. It was found that the polymer formulations provided significantly higher plasma levels and significantly lower brain tissue levels of drug than a control, in the form of a simple drug solution. Changing the depth of insertion of the cannula from 7 to 15mm, in order to reach the olfactory region in the nasal cavity significantly decreased plasma levels and significantly increased brain tissue levels of drug for the two formulations studied (1.0% pectin LM-12 and a simple drug solution). There was no significant difference between the drug availability for the bioadhesive formulation and the control in the brain when the longer cannula was used for administration. It is suggested that the conventional rat model is not suitable for evaluation of the effects of bioadhesive formulations in nose-to-brain delivery.

Symptom management and self-care for peripheral neuropathy in HIV/AIDS.

Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of peripheral neuropathy in HIV disease, sociodemographic and disease-related correlates and self-care strategies. A convenience sample of 1,217 respondents was recruited from data collection sites in several US cities, Puerto Rico, Colombia and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n=450) identified 20 self-care behaviors including complementary therapies, use of medications, exercise and rest and/or elevation of extremities. Ratings of frequency and effectiveness were also included. An activities checklist summarized into five categories of self-care behaviors including activities/thoughts, exercise, medications, complementary therapies and substance was used to determine self-care behaviors. Taking a hot bath was the most frequent strategy used by those with peripheral neuropathy (n=292) and received the highest overall rating of effectiveness of any self-management strategies included in this study at 8.1 (scale 1-10). Other self-care strategies to manage this symptom included: staying off the feet (n=258), rubbing the feet with cream (n=177), elevating the feet (n=236), walking (n=262), prescribed anti-epileptic agent (n=80), prescribed analgesics (n=84), over-the-counter medications (n=123), vitamin B (n=122), calcium supplements (n=72), magnesium (n=48), massage (n=156), acupuncture (n=43), reflexology (n=23) and meditation (n=80). Several behaviors that are often deemed unhealthy were included among the strategies reported to alleviate peripheral neuropathy including use of marijuana (n=67), cigarette smoking (n=139), drinking alcohol (n=81) and street drugs (n=30).

Distribution and clearance of bioadhesive formulations from the olfactory region in man: effect of polymer type and nasal delivery device.

There is an increasing need to identify novel approaches by which to improve the efficiency of drug transport from the nasal cavity (olfactory region) to the CNS, especially for treatment of central nervous system disorders. It is suggested, that one approach is the combination of active targeting of a bioadhesive formulation, that will retain the drug at the absorption site, potentially in combination with, an absorption enhancer. Two low methylated pectins, LM-5 and LM-12 were selected for evaluation as drug delivery systems, due to their ability to gel in the nasal cavity and their bioadhesive characteristics, together with chitosan G210, which acts both as a bioadhesive material and as an efficient absorption enhancer. It was found that all of the bioadhesive formulations were able to reach the olfactory region in the nasal cavity of human volunteers when delivered using a simple nasal drop device. Furthermore, the formulations displayed a significantly increased residence time on the epithelial surface. This was in contrast to a non-bioadhesive control delivered with the same device. In contrast, a pectin formulation administered with a nasal spray system did not show an increase in residence time in the olfactory region. It was further shown that the reproducibility of olfactory delivery of a polymer formulation was significantly better intra-subject than inter-subject.

Evaluation of bioadhesive polymers as delivery systems for nose to brain delivery: in vitro characterisation studies.

There is an increasing need for nasal drug delivery systems that could improve the efficiency of the direct nose to brain pathway especially for drugs for treatment of central nervous system disorders. Novel approaches that are able to combine active targeting of a formulation to the olfactory region with controlled release bioadhesive characteristics, for maintaining the drug on the absorption site are suggested. If necessary an absorption enhancer could be incorporated. Low methylated pectins have been shown to gel and be retained in the nasal cavity after deposition. Chitosan is known to be bioadhesive and also to work as an absorption enhancer. Consequently, two types of pectins, LM-5 and LM-12, together with chitosan G210, were selected for characterisation in terms of molecular weight, gelling ability and viscosity. Furthermore, studies on the in vitro release of model drugs from candidate formulations and the transport of drugs across MDCK1 cell monolayers in the presence of pectin and chitosan were also performed. Bioadhesive formulations providing controlled release with increased or decreased epithelial transport were developed. Due to their promising characteristics 3% LM-5, 1% LM-12 pectin and 1% chitosan G210 formulations were selected for further biological evaluation in animal models.

Homocysteine, estrogen and cognitive decline.

BACKGROUND: Factors that contribute to cognitive decline in women from midlife remain poorly understood. There are circumstantial data indicating a positive association between homocysteine and cognitive decline and that endogenous and exogenous estrogen may influence homocysteine levels. The aim of this review was to establish what is known of the relationships between cognitive change and homocysteine levels, and the impact of the menopause transition and exogenous estrogen on homocysteine levels. METHODS: We reviewed the recent published literature from 1993 to 2005 pertaining to the current understanding of the relationship(s) between plasma homocysteine levels and cognitive functioning and endogenous hormone levels and exogenous estrogen use in women. RESULTS: Hyperhomocysteinemia is consistently associated with cognitive decline. Dietary supplementation with vitamins may assist in normalizing homocysteine levels; however, there is no evidence that this results in favorable effects on cognition. Changes in endogenous estrogen levels are inversely associated with changes in serum homocysteine. Consistent with this, estrogen therapy is associated with reductions in plasma homocysteine, with the greatest effects reported in women with higher levels of homocysteine at baseline. Limited data indicate that tibolone is associated with little change in homocysteine. The use of raloxifene, the most studied selective estrogen receptor modulator, is associated with a modest reduction in homocysteine. CONCLUSIONS: There are data to suggest an underlying link between homocysteine levels and cognitive decline. There is also evidence for a link between both the menopause transition and use of exogenous estrogen therapy and homocysteine levels. Clinical data do not support a role for exogenous estrogen in the prevention of dementia in older women; however, the 'window of opportunity' theory suggests that there is a need for randomized controlled trials to evaluate the role of estrogen in the early postmenopausal years to protect against cognitive decline in later life.

Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000.

The role of dietary one-carbon determinants remains largely unexplored for non-Hodgkin's lymphoma (NHL). In a population-based case-control study of non-African-American adult (aged 20-74 years) women and men from four US Surveillance, Epidemiology, and End Results study centers (Detroit, Michigan; Iowa; Los Angeles, California; and Seattle, Washington; 1998-2000), the authors examined folate; vitamins B2, B6, and B12; methionine; and a one-carbon antagonist, alcohol, in 425 incident NHL cases and 359 controls who completed a detailed food frequency questionnaire. Adjusted odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Higher intake of one-carbon determinants from food was associated with a lower risk of NHL, but that for only vitamin B6 (highest vs. lowest quartile: odds ratio = 0.57, 95% confidence interval: 0.34, 0.95; p trend = 0.01) and methionine (odds ratio = 0.49, 95% confidence interval: 0.31, 0.76; p trend = 0.002) reached statistical significance. Folate from food was inversely associated with diffuse subtype (odds ratio = 0.47, 95% confidence interval: 0.23, 0.94; p trend = 0.03). The authors found no association between total (food plus supplement) vitamins and NHL. Nonusers of alcohol had an elevated NHL risk compared with users, and alcohol did not modify other nutrient-NHL associations. Findings suggest that one-carbon nutrients, particularly vitamin B6 and methionine, may be protective against NHL.

Pharmacokinetic and pharmacodynamic issues in the treatment of bacterial infectious diseases.

This review outlines some of the many factors a clinician must consider when selecting an antimicrobial dosing regimen for the treatment of infection. Integration of the principles of antimicrobial pharmacology and the pharmacokinetic parameters of an individual patient provides the most comprehensive assessment of the interactions between pathogen, host, and antibiotic. For each class of agent, appreciation of the different approaches to maximize microbial killing will allow for optimal clinical efficacy and reduction in risk of development of resistance while avoiding excessive exposure and minimizing risk of toxicity. Disease states with special considerations for antimicrobial use are reviewed, as are situations in which pathophysiologic changes may alter the pharmacokinetic handling of antimicrobial agents.

Process water treatment at the Ranger uranium mine, Northern Australia.

The conceptual development and piloting of an innovative water treatment system for process water produced by a uranium mine mill is described. The process incorporates lime/CO2 softening (Stage 1), reverse osmosis (Stage 2) and biopolishing (Stage 3) to produce water of quality suitable for release to the receiving environment. Comprehensive performance data are presented for each stage. The unique features of the proposed process are: recycling of the lime/CO2 softening sludge to the uranium mill as a neutralant, the use of power station off-gas for carbonation, the use of residual ammonia as the pH buffer in carbonation; and the recovery and recycling of ammonia from the RO reject stream.