DDT in zebra mussels from Lake Maggiore (N. Italy): level of contamination and endocrine disruptions

The DDT contamination of Lake Maggiore (Northern Italy) has been monitored since a serious pollution event occurred in 1996. To assess the environmental risk associated with this contamination, bioaccumulation data coupled with histopathological markers were evaluated on zebra mussel populations from two different contaminated sites from April 2001 to April 2002. Biomonitoring results showed high DDT pollution in 2001 because of a flood which transported DDTs still contained in the sediments of a polluted river to the lake. DDT concentrations reached values of 4-5 microg/g lipids, higher than those recorded in other industrialized countries but comparable to levels measured in developing ones. In the ovaries of the most highly polluted mussels, histological analyses showed a delay in oocyte maturation and a high incidence of pathological pictures mainly referable to oocyte degeneration and haemocytic infiltration. Moreover, despite the presence of mature sperms, in 2001 first male gamete release occurred about 2 months later than in females. These results indicated a neuroendocrine interference of DDT on Dreissena polymorpha reproduction and also showed that these invertebrates can be successfully used to evaluate ecological implications due to exposure to endocrine disruptors in freshwater environments.     

Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II major depressive episode: a randomized open-label study

OBJECTIVE: Practice guidelines for the initial treatment of bipolar II (BP II) major depressive episode (MDE) recommend mood stabilizer (MS) monotherapy or combined MS plus antidepressant drug (AD) therapy. We hypothesized that initial AD monotherapy would be superior to MS monotherapy for BP II MDE with a low hypomanic switch rate. METHODS: Bipolar II MDE patients were randomized to a 12-week open-label treatment with either venlafaxine monotherapy (n = 43) or lithium carbonate monotherapy (n = 40). The primary outcome measure was the 28-item Hamilton Depression Rating Scale (HAM-D 28). The secondary outcome measures included the Young Mania Rating Scale (YMRS), clinical global impressions severity and change ratings, and the proportion of patients classified as responder (with > or = 50% reduction in baseline HAM-D score) or as remitter (final HAM-D score, < or = 8). RESULTS: Thirty-four venlafaxine-treated patients (79.1%) and 15 lithium-treated patients (37.5%) completed the trial (P < 0.0005). Venlafaxine monotherapy produced a greater reduction in HAM-D 28 scores, with a difference in change of -6.57 points (95% confidence interval, -11.97 to -1.18) (P = 0.017) between treatment conditions. There was a greater proportion of venlafaxine-treated (vs lithium-treated) patients classified either as treatment responder (58.1% vs 20.0%; P < 0.0005) or as treatment remitter (44.2% vs 7.5%; P < 0.0005) for the HAM-D 28 scores. There was no significant increase in mean YMRS scores over time in the venlafaxine (vs lithium) treatment condition, and no significant increase in mean YMRS scores at any study visit compared with baseline for either treatment. CONCLUSIONS: Results from this study suggest that AD monotherapy with venlafaxine may be an effective initial therapy for BP II MDE with a low hypomanic switch rate.     

Importance of Bak for celecoxib-induced apoptosis

The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib constitutes the prototype of pro-apoptotic agents acting through the intrinsic death pathway in a Bcl-2 independent manner. To gain further insight into celecoxib-mediated apoptosis regulation at the level of the mitochondria we tested in how far the crucial pro-apoptotic Bcl-2 proteins Bak and Bax were involved using clones of the Bax-deficient Jurkat T-lymphoma cell model either expressing Bak (Jurkat Bak positive) or being negative for Bak (Jurkat Bak negative), or overexpressing Bcl-2 (Jurkat Bcl-2). Celecoxib induced substantial apoptosis in Jurkat Bak-positive cells. Overexpression of Bcl-2 had only limited protective effects. However, loss of Bak-expression conferred almost complete resistance of Jurkat cells to celecoxib-induced apoptosis. Neither enhanced celecoxib-concentrations nor prolonged incubation times were sufficient to normalize apoptotic rates upon celecoxib-treatment in these Bak/Bax-negative cells. In line with that observation, siRNA-mediated silencing of Bak in the Bak-positive Jurkat cells largely reduced the extent of celecoxib-induced cell death. Interestingly, in celecoxib-sensitive Bak-positive cells, celecoxib-treatment resulted in down-regulation of the anti-apoptotic Bcl-2 protein Mcl-1 which may contribute to celecoxib-mediated activation of Bak-dependent apoptosis. Taken together our data clearly show for the first time the functional relevance of Bak for celecoxib-induced apoptosis in Bax-deficient Jurkat T-lymphoma cells.     

Parenteral Soy Oil and Fish Oil Emulsions

Background: Parenteral nutrition (PN)–associated liver disease (PNALD) remains a significant cause of morbidity and mortality for neonates dependent on PN. Total fat emulsion dose and composition, particularly the large amount of ω‐6 long‐chain polyunsaturated fatty acids in plant oils, have been proposed as risk factors for PNALD. We hypothesized restriction of the dose of emulsion would prevent PNALD, regardless of the composition, but growth could be compromised. Methods: Using a neonatal piglet model, we compared conventional soy oil emulsion (Intralipid), dosed high (SO10, n = 8: 10 g/kg/d) and low (SO5, n = 6: 5 g/kg/d), with fish oil (Omegaven), dosed low (FO5, n = 8: 5 g/kg/d). Piglets were given isonitrogenous PN for 14 days. The normal range for all parameters was determined by measurement in equivalent aged sow‐reared piglets. Results: Bile flow was lower with high‐dose Intralipid, outside the normal range, while higher for the other groups (SO10, 5.4 µg/g; SO5, 8.6 µg/g; FO5, 13.4 µg/g; P = .010; normal range, 6.5–12.2 µg/g). Total body weight was low in all treatment groups (SO10, 4.4 kg; SO5, 4.5 kg; FO5, 5.0 kg; P = .038; normal range, 5.2–7.3 kg). Brain weight was not different between groups (SO10, 40.3 g; SO5, 36.0 g; FO5, 36.6 g; P = .122; normal range, 41.8–51.4 g). Corrected for body weight, brain weight was lowest in the fish oil group (SO10, 9.3 g/kg; SO5, 8.0 g/kg; FO5, 7.3 g/kg; P < .001; normal range, 5.9–9.0 g/kg). Conclusion: Low‐dose fat emulsions reduce the risk of developing PNALD. Further investigation of the risk to brain development in neonates exposed to dose restriction, particularly with fish oil, is required.     

Transition of stable patients from traditional anticoagulation clinic services to telephonic management

Background Outpatient warfarin dosing and monitoring with telephonic anticoagulation management (TAM) could be an effective alternative to other more labor intensive management models. Objectives To evaluate the time in therapeutic range (TTR) and number of extreme INR values (<1.5 or >4.5) of a telephonic system of warfarin management for stable patients who currently utilized traditional anticoagulation management services (AMSs). Method A retrospective, observational cohort with three groups (1) patients transitioned from an office-based anticoagulation clinic to TAM, (2) patients continuously enrolled in office-based AMS, (3) patients continuously managed by usual physician care without specialized anticoagulation services (UPC). Data was collected for six months before and six months after transition. Results All groups demonstrated decreased TTR from baseline to active phase, with the TAM and AMS groups showing similar magnitude of reduction (?10.61 and ?12.66% respectively) but UPC group producing a greater drop (?20.08%). The TAM and AMS groups had similar rates of extreme INR levels; UPC had higher numbers of extreme INRs in three of the four measurements. Conclusion Stable patients transitioned from office-based anticoagulation clinic to a telephonic model of management performed equally as well as those who continued traditional enrollment.     

Identification of new urinary gamma‐hydroxybutyric acid markers applying untargeted metabolomics analysis following placebo‐controlled administration to humans

Gamma‐hydroxybutyrate (GHB) is a short‐chain fatty acid that occurs naturally in the mammalian brain and is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock‐out drug in cases of drug‐facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 hours in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use. In the framework of a randomized, placebo‐controlled, crossover study in 20 healthy male volunteers, urine samples obtained 4.5 hours post‐administration were submitted to untargeted mass spectrometry [MS, quadrupole time of flight (QTOF)] analysis to identify possible new markers of GHB intake. MS data from four different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization) were filtered for significantly changed features applying univariate and multivariate statistics. From the resulting 42 compounds of interest, 8 were finally identified including conjugates of GHB with carnitine, glutamate, and glycine as well as the endogenous compounds glycolate and succinylcarnitine. While GHB conjugates were only detectable in the GHB, but not in the placebo group, glycolate and succinylcarnitine were present in both groups albeit significantly increased through GHB intake. Untargeted metabolomics proved as a suitable tool for the non‐hypothesis driven identification of new GHB markers. However, more studies on actual concentrations, detection windows, and stability will be necessary to assess the suitability of these markers for routine application.     

Using epidemiological data to model efficiency in reducing the burden of depression*

BACKGROUND: The Global Burden of Disease study has suggested that mental disorders are the leading cause of disability burden in the world. This study takes the leading cause of mental disorder burden, depression, and trials an approach for defining the present and optimal efficiency of treatment in an Australian setting. AIMS OF THE STUDY: To examine epidemiological and service use data for depression to trial an approach for modelling (i) the burden that is currently averted from current care, (ii) the burden that is potentially avertable from a hypothetical regime of optimal care, (iii) the efficiency or cost-effectiveness of both current and optimal services for depression and (iv) the potential of current knowledge for reducing burden due to depression, by applying the WHO five-step method for priorities for investment in health research and development. METHODS: Effectiveness and efficiency were calculated in disability adjusted life years (DALYs) averted by adjusting the disability weight for people who received efficacious treatment. Data on service use and treatment outcome were obtained from a variety of secondary sources, including the Australian National Survey of Mental Health and Wellbeing, and efficacy of individual treatments from published meta-analyses expressed in effect sizes. Direct costs were estimated from published sources. RESULTS: Fifty-five percent of people with depression had had some contact with either primary care or specialist services. Effective coverage of depression was low, with only 32% of cases receiving efficacious treatment that could have lessened their severity (averted disability). In contrast, a proposed model of optimal care for the population management of depression provided increased treatment contacts and a better outcome. In terms of efficiency, optimal care dominated current care, with more health gain for less expenditure (28 632 DALYs were averted at a cost of AUD295 million with optimal care, versus 19 297 DALYs averted at a cost of AUD720 million with current care). However, despite the existence of efficacious technologies for treating depression, only 13% of the burden was averted from present active treatment, primarily because of the low effective coverage. Potentially avertable burden is nearly three times this, if effective treatments can be delivered in appropriate amounts to all those who need it. DISCUSSION: This paper reports a method to calculate the burden currently averted from cross-sectional survey data, and to calculate the burden likely to be averted from an optimal programme estimated from randomized controlled trial data. The approach taken here makes a number of assumptions: that people are accurate in reporting their service use, that effect sizes are a suitable basis for modelling improvements in disability and that the method used to translate effect sizes to disability weight change is valid. The robustness of these assumptions is discussed. Nonetheless it would appear that while optimal care could do more than present services to reduce the burden of depression, current technologies for treating depression are insufficient. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: There is an urgent need to educate both clinicians (primary and specialist) and the general public in the effective treatments that are available for depression. IMPLICATIONS FOR HEALTH POLICIES: Over and above implementing treatments of known efficacy, more powerful technologies are needed for the prevention and treatment of depression. IMPLICATIONS FOR FURTHER RESEARCH: Modelling burden averted from a variety of secondary sources can introduce bias at many levels. Future research should examine the validity of approaches that model reductions in disability burden. A powerful treatment to relieve depression and prevent relapse is needed.     

Insights in Public Health: Initiating Bicycle Sharing in Hawai‘i: Lessons Learned from a Small Pilot Bike Share Program

In 2011, a small pilot bike share program was established in the town core of Kailua, Hawai‘i, with funding from the Hawai‘i State Department of Health. The Kailua system consisted of two stations with 12 bicycles, and the goal was to secure additional funding to expand the station network in the future. Community feedback consistently indicated support for the bike share program. However, system metrics showed low levels of usage, averaging 41.5 rides per month (2011–2014). From observational data, users were primarily tourists. With minimal local staff, the bike share program had limited resources for promotion and education, which may have hindered potential use by local residents. Management of station operations and bike maintenance were additional, ongoing barriers to success. Despite the challenges, the pilot bike share program was valuable in several ways. It introduced the bike share concept to Hawai‘i, thereby helping to build awareness and connect an initial network of stakeholders. Furthermore, the pilot bike share program informed the development of a larger bike share program for urban Honolulu. As limited information exists in the literature about the experiences of smaller bike share programs and their unique considerations, this article shares lessons learned for other communities interested in starting similar bike share programs.