Chlorate has become a concern in the food and beverage sector, related to chlorine sanitizers in industrial food production and water treatment. It is of particular concern to regulatory bodies due ...to the negative health effects of chlorate exposure. This study investigated the fate of chlorate in raw milk and isolated bacterial strains of interest responsible for chlorate breakdown. Unpasteurized milk was demonstrated to have a chlorate-reducing capacity, breaking down enriched chlorate to undetectable levels in 11 days. Further enrichment and isolation using conditions specific to chlorate-reducing bacteria successfully isolated three distinct strains of
. Chlorate-reducing bacteria were observed to grow in a chlorate-enriched medium with lactate as an electron donor. All isolated strains were demonstrated to reduce chlorate in liquid medium; however, the exact mechanism of chlorate degradation was not definitively identified in this study.
In this study, hypotheses were tested that the quality of leader-member exchanges (LMX) depends on congruity of values between leader and member. Data on negotiating latitude and personal values were ...gathered from 160 members of 30 work groups in Australian organizations. Factor analysis revealed 5 value dimensions: Freedom, Achievement, Mateship, Obedience, and Coping. Analyses of variance supported the hypothesis that LMX quality is higher when leaders and members share achievement and obedience values. Subsequent exploratory analysis, however, indicated that a more complex model based on compatibility of leader authority and member affiliation values may provide a more complete representation.
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BFBNIB, CEKLJ, DOBA, FSPLJ, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Female Sprague-Dawley rats were injected with the noncompetitive
N
-methyl-
D
-aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in spatial working memory (WM) and reference ...memory (RM) procedures in an 8-arm radial maze. MK-801 impaired RM and WM acquisition but not performance when rats were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr delay between the first and last 2 correct WM choices impaired long-term WM. MK-801 impaired WM performance in trained rats only when rats were tested in a new environment. Thus, 2 mechanisms may be required for relational memory: an NMDA-dependent mechanism for acquiring long-term spatial representations and an NMDA-insensitive mechanism for operating on these stored representations.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Early‐adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual‐level data ...from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18–24 years and other breast cancer risk factors showed that weight gain from ages 18–24 to 35–44 or to 45–54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.95–0.98) and with oestrogen‐receptor(ER)‐positive breast cancer (HR per 5 kg to ages 45–54: 0.96, 95% CI: 0.94–0.98). Weight gain from ages 25–34 was inversely associated with ER‐positive breast cancer only and weight gain from ages 35–44 was not associated with risk. None of these weight gains were associated with ER‐negative breast cancer. Weight loss was not consistently associated with overall or ER‐specific risk after adjusting for initial weight. Weight increase from early‐adulthood to ages 45–54 years is associated with a reduced premenopausal breast cancer risk independently of early‐adulthood weight. Biological explanations are needed to account for these two separate factors.
What's new?
Body weight in childhood and early adulthood plays a key role in determining premenopausal breast cancer risk but little is conclusively known about how subsequent weight changes affect this risk. Here the authors pooled results from existing studies on weight changes and breast cancer risk including more than 600,000 premenopausal women. The results show that weight gain >10–15 kg from early adulthood on lowers the risk of developing premenopausal breast cancer, providing further evidence of body weight as an important determinant of breast cancer risk.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Context:
Treatment of X-linked hypophosphatemia (XLH) with active vitamin D metabolites and phosphate can partially correct skeletal deformities. It is unclear whether therapy influences the ...occurrence of two major long-term morbidities in XLH: enthesopathy and dental disease.
Objective:
The objective of the study was to investigate the relationship between treatment and enthesopathy and dental disease in adult XLH patients.
Design:
The study was designed as observational and cross-sectional.
Setting:
The study was conducted at an academic medical center's hospital research unit.
Participants:
Fifty-two XLH patients aged 18 years or older at the time of the study participated in the study.
Interventions:
There were no interventions.
Main Outcome Measures:
The number of enthesopathy sites identified by radiographic skeletal survey and dental disease severity (more than five or five or fewer dental abscesses), identified historically, were measured.
Methods:
Associations between proportion of adult life and total life with treatment and number of enthesopathy sites were assessed using multiple linear regression, whereas associations between these exposure variables and dental disease severity were assessed using multiple logistic regression. All models were adjusted for confounding factors.
Results:
Neither proportion of adult nor total life with treatment was a significant predictor of extent of enthesopathy. In contrast, both of these treatment variables were significant predictors of dental disease severity (multivariate-adjusted global P = .0080 and P = .0010, respectively). Participants treated 0% of adulthood were more likely to have severe dental disease than those treated 100% of adulthood (adjusted odds ratio 25 95% confidence interval 1.2–520). As the proportion of adult life with treatment increased, the odds of having severe dental disease decreased (multivariate-adjusted P for trend = .015).
Conclusions:
Treatment in adulthood may not promote or prevent enthesopathy; however, it may be associated with a lower risk of experiencing severe dental disease.
The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of ...neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel α2 -δ ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.
The oral thrombopoietin receptor agonist eltrombopag is approved for treatment of adults with chronic immune thrombocytopenia. In the PETIT trial, we aimed to investigate the efficacy and safety of ...eltrombopag in children with persistent or chronic immune thrombocytopenia.
PETIT was a three-part, randomised, multicentre, placebo-controlled study done at 22 centres in the USA, UK, Canada, Spain, France, and the Netherlands. Patients aged 1-17 years with immune thrombocytopenia lasting for 6 months or longer and platelets less than 30 × 10(9) per L who had received at least one previous treatment were enrolled. We enrolled patients into three cohorts consisting of patients aged 12-17, 6-11, and 1-5 years. We established patients' starting doses with an open-label, dose-finding phase with five patients in each cohort. During the dose-finding phase, patients aged 6-17 years started eltrombopag at 25 mg once per day (12·5 mg for those weighing <27 kg) and patients aged 1-5 years received 0·7 mg/kg per day to a maximum of 2 mg/kg unless otherwise approved. We permitted dose adjustments on the basis of platelet response up to a maximum dosage of 75 mg per day. Additional patients were then recruited and randomly assigned (2:1) to receive either eltrombopag or placebo tablets (or oral suspension formulation if aged 1-5 years) once per day for 7 weeks at the previously established doses. Starting doses for the double-blind phase were 37·5 mg/day for patients aged 12-17 years; 50 mg/day for patients weighing 27 kg or more (25 mg for east Asian patients) and 25 mg/day for patients weighing less than 27 kg (12·5 mg once per day for east Asian patients) for patients aged 6-11 years; and 1·5 mg/kg once per day (0·8 mg/kg once per day for east Asian patients) for patients aged 1-5 years. Randomisation was done by the GlaxoSmithKline Registration/Medication Ordering System and both patients and study personnel were masked to treatment assignments. Patients who completed treatment were then enrolled into an open-label phase and all patients could receive up to 24 weeks of eltrombopag. The primary outcome was the proportion of patients achieving a platelet count of 50 × 10(9) per L or more at least once from weeks 1-6 (days 8 to 43) of the randomised phase of the study in the absence of rescue therapy. We assessed efficacy in the intent-to-treat population, which consisted of all patients assigned to treatment, and we assessed safety in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT00908037.
Between Oct 2, 2009, and June 22, 2011, we recruited 15 patients, with five patients in each age cohort, into the open-label dose-finding phase who did not progress into the double-blind phase. From March 17, 2010, to Jan 15, 2013, we randomly assigned 67 patients to treatment, with 45 patients assigned to receive eltrombopag (16 children aged 12-17 years, 19 aged 6-11 years, and ten aged 1-5 years) and 22 to receive placebo (eight children aged 12-17 years, nine aged 6-11 years, and five aged 1-5 years). However, two patients assigned to receive eltrombopag did not receive the study drug and one was lost to follow-up, and one patient assigned to receive placebo was given eltrombopag. From weeks 1 to 6, 28 (62%) patients who received eltrombopag, compared with seven (32%) who received placebo, achieved the primary endpoint of platelet count 50 × 10(9) per L or more at least once without rescue (odds ratio 4·31, 95% CI 1·39-13·34, p=0·011). The most common adverse events with eltrombopag were headache (13 30% patients receiving eltrombopag vs nine 43% patients receiving placebo), upper respiratory tract infection (11 25% patients vs two 10% patients), and diarrhoea (seven 16% patients vs one 5% patient). Grade 3 or 4 adverse events occurred in five (11%) patients receiving eltrombopag and four (19%) patients receiving placebo, and serious adverse events (four 9% patients receiving eltrombopag and two (10%) patients receiving placebo) were similarly infrequent in both groups. No thrombotic events or malignancies occurred. Increased alanine aminotransferase concentrations caused two (3%) of 65 patients to discontinue eltrombopag in the open-label phase.
Our results showed that eltrombopag could be used to increase platelet counts and reduce clinically significant bleeding in children with persistent or chronic immune thrombocytopenia. Prevalence of increased liver laboratory values was similar to that seen in adults.
GlaxoSmithKline.
Objectives
To identify determinants of incident malnutrition in community‐dwelling older adults.
Design
Meta‐analysis of 6 community‐based longitudinal datasets with follow‐up of 1 to 3 years.
...Setting
Datasets from MaNuEL (MalNutrition in the Elderly) partners were included: 3 studies from Germany and 1 each from Ireland, the Netherlands, and New Zealand.
Participants
community‐dwelling adults aged 65 and older (N=4,844).
Measurement
The same definition of incident malnutrition was used for all cohorts (body mass index < 20.0 kg/m2 at follow‐up or weight loss ≥10 % between baseline and follow‐up). Twenty‐one potential baseline determinants from 7 domains (demographic, nutritional, lifestyle, social, psychological, physical functioning, medical) and 2 follow‐up variables (hospitalization, falls) were harmonized for all studies. Binary logistic regression analyses were performed to assess the association between each variable, adjusted for specific confounders, and incident malnutrition. Combined odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random‐effects meta‐analyses.
Results
Studies included between 209 and 1,841 participants without malnutrition at baseline; mean age ranged from 71.7 to 84.6. Incidence of malnutrition varied from 5.1% and 17.2%. Meta‐analyses identified 6 variables as independent determinants of incident malnutrition; with increasing age, the risk of developing malnutrition increased continuously. Unmarried, separated, or divorced participants were more likely to develop malnutrition than married participants, whereas no association was found for widowed participants. Participants with difficulty walking (OR=1.41, 95% CI=1.06–1.89) or difficulty climbing stairs (OR=1.45, 95% CI=1.14–1.85) and those who were hospitalized before baseline (OR=1.49, 95% CI=1.25–1.76) and during follow‐up (OR=2.02, 95% CI=1.41–2.88) had higher odds of incident malnutrition.
Conclusion
In this harmonized meta‐analysis based on prospective data of older, community‐dwelling adults, age, marital status, limitations with walking and climbing stairs, and hospitalization were identified as determinants of incident malnutrition. J Am Geriatr Soc 66:2335–2343, 2018.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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