bluuebunny/crossref_metadata_2025 huggingface dataset:
Mild hypothermia of 34°C reduces side effects of rt-PA treatment after thromboembolic stroke in rats
Authors: Kallmünzer Bernd , Schwab Stefan , Kollmar Rainer
Published: March 2012

Background

Hypothermia is neuroprotective in experimental stroke and may extend the so far limited therapeutic time window for thrombolysis. Therefore, hypothermia of 34°C and its effects on delayed thrombolysis including reperfusion-associated injury were investigated in a model of thromboembolic stroke (TE).

Methods

Male Wistar rats (n = 48) were subjected to TE. The following treatment groups were investigated: control group - normothermia (37°C); thrombolysis group - rt-PA 90 min after TE; hypothermia by 34°C applied 1.5 to 5 hours after TE; combination therapy- hypothermia and rt-PA. After 24 hours infarct size, brain edema and neuroscore were assessed. Protein markers for inflammation and adhesion, gelatinase activity, and blood brain barrier (BBB) disruption were determined. MRI-measurements investigated infarct evolution and blood flow parameters.

Results

The infarct volume and brain swelling were smaller in the hypothermia group compared to the other groups (p < 0.05 to p < 0.01). Thrombolysis resulted in larger infarct and brain swelling than all others. Hypothermia in combination with thrombolysis reduced these parameters compared to thrombolysis (p < 0.05). Moreover, the neuroscore improved in the hypothermia group compared to control and thrombolysis. Animals of the combination therapy performed better than after thrombolysis alone (p < 0.05). Lower serum concentration of sICAM-1, and TIMP-1 were shown for hypothermia and combination therapy. Gelatinase activity was decreased by hypothermia in both groups.

Conclusions

Therapeutic hypothermia reduced side-effects of rt-PA associated treatment and reperfusion in our model of TE.
Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice
Authors: Wang Bei , Zaidi Neeha , He Li-Zhen , Zhang Li , Kuroiwa Janelle MY , Keler Tibor , Steinman Ralph M
Published: March 2012

Introduction

Given their relative simplicity of manufacture and ability to be injected repeatedly, vaccines in a protein format are attractive for breast and other cancers. However, soluble human epidermal growth factor receptor (HER2)/neu protein as a vaccine has not been immunogenic. When protein is directly targeted to antigen uptake receptors, such as DEC205 (DEC), efficient processing and presentation of antigen take place. The aim of this study was to determine the immunogenicity of a HER2 protein vaccine that directly targets to DEC+ dendritic cells (DCs) in a mouse breast cancer model.

Methods

We genetically engineered the HER2 extracellular domain into a monoclonal antibody specific for DEC (DEC-HER2). Mice of various genetic backgrounds were immunized with DEC-HER2 in combination with DC maturation stimuli (poly IC ± CD40 Ab). Vaccine-induced T cell immunity was determined by analyzing the ability of CD4+/CD8+ T cell to produce interferon (IFN)-gamma and proliferate upon antigen rechallenge. Sera were assessed for the presence of antigen specific antibody (Ab). For vaccine efficacy, FVB/N mice were immunized with DEC-HER2 in combination with poly IC and protection against neu-expressing mammary tumors was assessed. Protection mechanisms and tumor-specific T cell responses were also evaluated.

Results

We demonstrate that DEC-HER2 fusion mAb, but not Ctrl Ig-HER2, elicits strong, broad and multifunctional CD4+ T cell immunity, CD8+ T cell responses, and humoral immunity specific for HER2 antigen. Cross-reactivity to rat neu protein was also observed. Importantly, mice xeno-primed with DEC-HER2 were protected from a neu-expressing mammary tumor challenge. Both CD4+ and CD8+ T cells mediated the tumor protection. Robust anti-tumor T cell immunity was detected in tumor protected mice.

Conclusions

Immunization of mice with HER2 protein vaccine targeting DEC+ DCs in vivo induced high levels of T- and B-cell immunity. Non-targeted HER2 protein was poorly immunogenic for CD4+ and CD8+ T cells. This vaccination approach provided long-term survival benefit for mice challenged with neu-expressing tumor following as little as 2.7 μg of HER2 protein incorporated in the vaccine. Vaccine-induced CD4+ and CD8+ T cells were both essential for tumor protection. This immunization strategy demonstrates great potential towards the development of vaccines for breast cancer patients.
Medical emergencies on board commercial airlines: is documentation as expected?
Authors: Sand Michael , Morrosch Stephan , Sand Daniel , Altmeyer Peter , Bechara Falk G
Published: March 2012

Introduction

The purpose of this study was to perform a descriptive, content-based analysis on the different forms of documentation for in-flight medical emergencies that are currently provided in the emergency medical kits on board commercial airlines.

Methods

Passenger airlines in the World Airline Directory were contacted between March and May 2011. For each participating airline, sample in-flight medical emergency documentation forms were obtained. All items in the sample documentation forms were subjected to a descriptive analysis and compared to a sample "medical incident report" form published by the International Air Transport Association (IATA).

Results

A total of 1,318 airlines were contacted. Ten airlines agreed to participate in the study and provided a copy of their documentation forms. A descriptive analysis revealed a total of 199 different items, which were summarized into five sub-categories: non-medical data (63), signs and symptoms (68), diagnosis (26), treatment (22) and outcome (20).

Conclusions

The data in this study illustrate a large variation in the documentation of in-flight medical emergencies by different airlines. A higher degree of standardization is preferable to increase the data quality in epidemiologic aeromedical research in the future.
Cell surface localization and release of the candidate tumor suppressor Ecrg4 from polymorphonuclear cells and monocytes activate macrophages
Authors: Baird Andrew , Coimbra Raul , Dang Xitong , Lopez Nicole , Lee Jisook , Krzyzaniak Michael , Winfield Robert , Potenza Bruce , Eliceiri Brian P
Published: March 2012

We identified fresh human leukocytes as an abundant source of the candidate epithelial tumor suppressor gene, Ecrg4, an epigenetically regulated gene, which unlike other tumor suppressor genes, encodes an orphan-secreted, ligand-like protein. In human cell lines, Ecrg4 gene expression was low, Ecrg4 protein undetectable, and Ecrg4 promoter hypermethylation high (45–90%) and reversible by the methylation inhibitor 5-AzaC. In contrast, Ecrg4 gene expression in fresh, normal human PBMCs and PMNs was 600–800 times higher than in cultured cell lines, methylation of the Ecrg4 promoter was low (<3%), and protein levels were readily detectable in lysates and on the cell surface. Flow cytometry, immunofluorescent staining, and cell surface biotinylation established that full-length, 14-kDa Ecrg4 was localized on PMN and monocyte cell surfaces, establishing that Ecrg4 is a membrane-anchored protein. LPS treatment induced processing and release of Ecrg4, as detected by flow and immunoblotting, whereas an effect of fMLF treatment on Ecrg4 on the PMN cell surface was detected on the polarized R2 subpopulation of cells. This loss of cell surface Ecrg4 was associated with the detection of intact and processed Ecrg4 in the conditioned media of fresh leukocytes and was shown to be associated with the inflammatory response that follows severe, cutaneous burn injury. Furthermore, incubation of macrophages with a soluble Ecrg4-derived peptide increased the P-p65, suggesting that processing of an intact sentinel Ecrg4 on quiescent circulating leukocytes leads to processing from the cell surface following injury and macrophage activation.
Minireview: Animal Models and Mechanisms of Ovarian Cancer Development
Authors: Mullany Lisa K. , Richards JoAnne S.
Published: March 2012

Ovarian cancer in women is a complex and deadly disease, where the molecular events that initiate and control tumor formation remain poorly defined. Therefore, mouse models provide one approach for determining the mechanisms by which specific oncogenic factors cause ovarian surface epithelial cell and granulosa cell transformation. This minireview summarizes the phenotypes of current mouse models that have been generated and some of the underlying mechanisms they have provided.
Climate change and cutaneous water loss of birds
Authors: Williams Joseph B. , Muñoz-Garcia Agustí , Champagne Alex
Published: March 2012

There is a crucial need to understand how physiological systems of animals will respond to increases in global air temperature. Water conservation may become more important for some species of birds, especially those living in deserts. Lipids of the stratum corneum (SC), the outer layer of the epidermis, create the barrier to water vapor diffusion, and thus control cutaneous water loss (CWL). An appreciation of the ability of birds to change CWL by altering lipids of the skin will be important to predict responses of birds to global warming. The interactions of these lipids are fundamental to the modulation of water loss through skin. Cerebrosides, with their hexose sugar moiety, are a key component of the SC in birds, but how these lipids interact with other lipids of the SC, or how they form hydrogen bonds with water molecules, to form a barrier to water vapor diffusion remains unknown. An understanding of how cerebrosides interact with other lipids of the SC, and of how the hydroxyl groups of cerebrosides interact with water molecules, may be a key to elucidating the control of CWL by the SC.
Relationship between colouration and body condition in a crab spider that lures pollinators
Authors: Gawryszewski Felipe M. , Llandres Ana L. , Herberstein Marie E.
Published: March 2012

Sit-and-wait predators have evolved several traits that increase the probability of encountering prey, including lures that attract prey. Although most crab spiders (Thomisidae) are known by their ability to change colour in order to match the background, a few use a different strategy. They are UV-reflective, creating a colour contrast against UV-absorbing flowers that is attractive for pollinators. The nature of the relationship between colour contrast and foraging success is unknown, as is how spiders trade off the potential costs and benefits of strong colour contrast. Therefore, this study investigated the relationship between spider colouration, foraging success and background colouration in a crab spider species known to lure pollinators via UV reflectance (Thomisus spectabilis). Field data revealed that spider body condition – a proxy of past foraging success – is positively related to overall colour contrast. We experimentally tested the effect of satiation and background colour on spider colour change. Throughout the experiment, spiders changed their colour contrast regardless of their food intake, suggesting that colour contrast and the UV component contributing to overall contrast are not caused by spider condition. Although spiders responded to different backgrounds by subtly changing their body colour, this did not result in colour matching. We believe that the observed variation in colour contrast and hence conspicuousness in the field, coupled with the spiders’ reaction to our manipulation, could be the result of plasticity in response to prey.
Non-linear scaling of oxygen consumption and heart rate in a very large cockroach species (Gromphadorhina portentosa): correlated changes with body size and temperature
Authors: Streicher Jeffrey W. , Cox Christian L. , Birchard Geoffrey F.
Published: March 2012

Although well documented in vertebrates, correlated changes between metabolic rate and cardiovascular function of insects have rarely been described. Using the very large cockroach species Gromphadorhina portentosa, we examined oxygen consumption and heart rate across a range of body sizes and temperatures. Metabolic rate scaled positively and heart rate negatively with body size, but neither scaled linearly. The response of these two variables to temperature was similar. This correlated response to endogenous (body mass) and exogenous (temperature) variables is likely explained by a mutual dependence on similar metabolic substrate use and/or coupled regulatory pathways. The intraspecific scaling for oxygen consumption rate showed an apparent plateauing at body masses greater than about 3 g. An examination of cuticle mass across all instars revealed isometric scaling with no evidence of an ontogenetic shift towards proportionally larger cuticles. Published oxygen consumption rates of other Blattodea species were also examined and, as in our intraspecific examination of G. portentosa, the scaling relationship was found to be non-linear with a decreasing slope at larger body masses. The decreasing slope at very large body masses in both intraspecific and interspecific comparisons may have important implications for future investigations of the relationship between oxygen transport and maximum body size in insects.
Gearing for speed slows the predatory strike of a mantis shrimp
Authors: McHenry Matthew J. , Claverie Thomas , Rosario Michael V. , Patek S. N.
Published: March 2012

The geometry of an animal’s skeleton governs the transmission of force to its appendages. Joints and rigid elements that create a relatively large output displacement per unit input displacement have been considered to be geared for speed, but the relationship between skeletal geometry and speed is largely untested. The present study explored this subject with experiments and mathematical modeling to evaluate how morphological differences in the raptorial appendage of a mantis shrimp (Gonodactylus smithii) affect the speed of its predatory strike. Based on morphological measurements and material testing, we computationally simulated the transmission of the stored elastic energy that powers a strike and the drag that resists this motion. After verifying the model’s predictions against measurements of strike impulse, we conducted a series of simulations that varied the linkage geometry, but were provided with a fixed amount of stored elastic energy. We found that a skeletal geometry that creates a large output displacement achieves a slower maximum speed of rotation than a low-displacement system. This is because a large displacement by the appendage causes a relatively large proportion of its elastic energy to be lost to the generation of drag. Therefore, the efficiency of transmission from elastic to kinetic energy mediates the relationship between the geometry and the speed of a skeleton. We propose that transmission efficiency plays a similar role in form–function relationships for skeletal systems in a diversity of animals.
Octopamine improves learning in newly emerged bees but not in old foragers
Authors: Behrends Andreas , Scheiner Ricarda
Published: March 2012

Honey bees (Apis mellifera) are well known for their excellent learning abilities. Although most age groups learn quickly to associate an odor with a sucrose reward, newly emerged bees and old foragers often perform poorly. For a long time, the reason for the poor learning performance of these age groups was unclear. We show that reduced sensitivity for sucrose is the cause for poor associative learning in newly emerged bees but not in old foragers. By increasing the sensitivity for sucrose through octopamine, we selectively improved the learning performance of insensitive newly emerged bees. Interestingly, the learning performance of foragers experiencing the same treatment remained low, despite the observed increase in sensitivity for the reward. We thus demonstrate that increasing sensitivity for the reward can improve the associative learning performance of bees when they are young but not when they had foraged for a long time. Importantly, octopamine can have very different effects on bees, depending on their initial sensory sensitivity. These differential effects of octopamine have important consequences for interpreting the action of biogenic amines on insect behavior.
Expression of SERCA and phospholamban in rainbow trout (Oncorhynchus mykiss) heart: comparison of atrial and ventricular tissue and effects of thermal acclimation
Authors: Korajoki Hanna , Vornanen Matti
Published: March 2012

In the heart of rainbow trout (Oncorhynchus mykiss), the rate of contraction and Ca2+ uptake into the sarcoplasmic reticulum (SR) are faster in atrial than ventricular muscle, and contraction force relies more on SR Ca2+ stores after acclimation to cold. This study tested the hypothesis that differences in contractile properties and Ca2+ regulation between atrial and ventricular muscle, and between warm-(WA) and cold-acclimated (CA) trout hearts, are associated with differences in expression of sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) and/or phospholamban (PLN), an inhibitor of the cardiac SERCA. Quantitative PCR (SERCA only) and antibodies raised against SERCA and PLN were used to determine abundances of SERCA2 transcripts and SERCA and PLN proteins, respectively, in atrium and ventricle of trout acclimated to cold (+4°C, CA) and warm (+18°C, WA) temperatures. Expression of SERCA2 transcripts was 1.6 and 2.1 times higher in atrium than ventricle of WA and CA trout, respectively (P<0.05). At the protein level, differences in SERCA expression between atrium and ventricle were 6.1- and 23-fold for WA and CA trout, respectively (P<0.001). Acclimation to cold increased SERCA2 transcripts 2.6- and 2.0-fold in atrial and ventricular muscle, respectively (P<0.05). At the protein level, cold-induced elevation of SERCA (4.6-fold) was noted only in atrial (P<0.05) but not in ventricular tissue (P>0.05). The expression pattern of PLN was similar to that of the SERCA protein, but chamber-specific and temperature-induced differences were much smaller than in the case of SERCA. In the ventricle, PLN/SERCA ratio was 2.1 and 7.0 times higher than in the atrium for WA and CA fish, respectively. These findings are consistent with the hypothesis that low PLN/SERCA ratio in atrial tissue enables faster SR Ca2+ reuptake and thus contributes to faster kinetics of contraction in comparison with ventricular muscle. Similarly, cold-induced decrease in PLN/SERCA ratio may be associated with faster contraction kinetics of the CA trout heart, in particular in the atrial muscle.
Development of agonistic encounters in dominance hierarchy formation in juvenile crayfish
Authors: Sato Daisuke , Nagayama Toshiki
Published: March 2012

We have characterized the behavioural patterns of crayfish during agonistic bouts between groups of crayfish of four different body lengths (9–19, 20–32, 41–48 and 69–75 mm) to characterize changes in the patterns of agonistic encounter during development. The behaviour of both dominant and subordinate animals was analysed by single frame measurement of video recordings. Behavioural acts that occurred during agonistic bouts were categorized as one of seven types: capture, fight, contact, approach, retreat, tailflip and neutral. Dominant–subordinate relationships were formed between juvenile crayfish as early as the third stage of development. Patterns of agonistic bouts to determine social hierarchy became more aggressive during development. The dominant–subordinate relationship was usually determined after contact in crayfish of less than 20 mm and 20–32 mm in length, while several bouts of fights were necessary for crayfish of 41–48 and 69–75 mm in length. Furthermore, social hierarchy was formed more rapidly in small crayfish. In larger animals, the number of approaches by dominant animals that promoted retreat in subordinate animals increased after the establishment of the winner–loser relationship. In smaller crayfish, in contrast, no measurable changes in these behaviour patterns were observed before and after the establishment of the winner–loser relationship. With increasing body size, the probability of tailflips decreased while that of retreats increased as the submissive behavioural act of subordinate animals.
Effects of night-time warming on temperate ectotherm reproduction: potential fitness benefits of climate change for side-blotched lizards
Authors: Clarke Donald N. , Zani Peter A.
Published: March 2012

Temperate ectotherms, especially those at higher latitudes, are expected to benefit from climate warming, but few data yet exist to verify this prediction. Furthermore, most previous studies on the effects of climate change utilized a model of uniform annual change, which assumes that temperature increases are symmetric on diurnal or seasonal time scales. In this study, we simulated observed trends in the asymmetric alteration of diurnal temperature range by increasing night-time temperatures experienced by female lizards during their ovarian cycle as well as by the resulting eggs during their incubation. We found that higher night-time temperatures during the ovarian cycle increased the probability of reproductive success and decreased the duration of the reproductive cycle, but did not affect embryo stage or size at oviposition, clutch size, egg mass or relative clutch mass. Furthermore, higher incubation temperatures increased hatchling size and decreased incubation period but had no effect on incubation success. Subsequent hatchlings were more likely to survive winter if they hatched earlier, though our sample size of hatchlings was relatively small. These findings indicate that higher night-time temperatures mainly affect rate processes and that certain aspects of life history are less directly temperature dependent. As our findings confirm that climate warming is likely to increase the rate of development as well as advance reproductive phenology, we predict that warmer nights during the breeding season will increase reproductive output as well as subsequent survival in many temperate ectotherms, both of which should have positive fitness effects.
Polycystic Ovary Syndrome and Chronic Inflammation: Pharmacotherapeutic Implications
Authors: Sirmans Susan Maureen , Weidman-Evans Emily , Everton Victoria , Thompson Daniel
Published: March 2012

Objective:

To examine the relationship between polycystic ovary syndrome (PCOS), cardiovascular risk factors, cardiovascular disease (CVD), and chronic inflammation and analyze data regarding pharmacologic therapies that are recommended to reduce CVD risk in PCOS and the impact of those therapies on chronic inflammation.

Data Sources:

A search of MEDLINE (1950-October 2011) was conducted to identify clinical studies pertaining to the identification and treatment of CVD and chronic low-grade inflammation in PCOS, Search terms included polycystic ovary syndrome, cardiovascular disease, inflammation, metformin, thiazolidinedione, and statin. Bibliographies of these studies and review articles were also examined.

Study Selection and Data Extraction:

English-language clinical studies evaluating the effect of metformin, thiazolidinediones, and statins on inflammatory markers, endothelial function, adhesion molecules, fibrinolysis, cytokines, and adipokines in PCOS were included.

Data Synthesis:

Women with PCOS have an increased prevalence of many cardiovascular risk factors including obesity, android fat distribution, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, hypertension, and metabolic syndrome. Markers of chronic low-grade inflammation, which are associated with an increased risk of CVD, are also elevated in PCOS. Clinical guidelines recommend the use of insulin sensitizers and statins to prevent CVD in some patients with PCOS. Current literature indicates that each of these medication classes has beneficial effects on inflammation, as well. Although there are currently no studies to determine whether these treatments decrease CVD in PCOS, it can be hypothesized that drugs impacting chronic inflammation may reduce cardiovascular risk. Some studies show that metformin, thiazolidinediones, and statins have beneficial effects on inflammatory markers in PCOS; however, the data are inconsistent.

Conclusions:

There is insufficient information to recommend any pharmacologic therapies for their antiinflammatory effects in PCOS in the absence of other indications such as diabetes and dyslipidemia.
Intravenous Neostigmine for Postoperative Acute Colonic Pseudo-Obstruction
Authors: Elsner Jamie L , Smith Janessa M , Ensor Christopher R
Published: March 2012

Objective:

To review the literature on the safety and effectiveness of neostigmine for the treatment of postoperative acute colonic pseudo-obstruction.

Data Sources:

The MEDLINE/PubMed, EMBASE, and Cochrane databases from November 1969 to November 2011 were queried for articles published in English, using the search terms neostigmine, acute colonic pseudo-obstruction, postoperative, surgery, and Ogilvie syndrome.

Study Selection and Data Extraction:

All relevant original studies, meta-analyses, systematic reviews, guidelines, and review articles were assessed for inclusion. References from pertinent articles were examined for additional content not found during the initial search.

Data Synthesis:

Neostigmine may provide an effective treatment option for postoperative acute colonic pseudo-obstruction (ACPO) after conservative treatment measures have failed. One randomized controlled trial, 8 prospective and 3 retrospective observational studies, and 9 case reports evaluated neostigmine for ACPO. Included studies were limited by small sample sizes and heterogeneous populations not focused on postoperative patients, use of adjuvant agents, and lack of a consistent neostigmine regimen.

Conclusions:

Neostigmine may be a safe and effective treatment option for postoperative ACPO; however, current data do not support its use as a first-line intervention. Prospective and retrospective studies have demonstrated improvement in clinical symptoms, reduction in time to resolution, and reduction of recurrence for patients who failed conservative management. Prospective clinical trial data that evaluate early neostigmine versus conservative management are critically needed to determine neostigmine's role as a first-line therapy for ACPO.
Effect of Medication Reconciliation on Medication Costs After Hospital Discharge in Relation to Hospital Pharmacy Labor Costs
Authors: Karapinar-Çarkit Fatma , Borgsteede Sander D , Zoer Jan , Egberts Toine CG , van den Bemt Patricia MLA , Tulder Maurits van
Published: March 2012

Background:

Medication reconciliation aims to correct discrepancies in medication use between health care settings and to check the quality of pharmacotherapy to improve effectiveness and safety. In addition, medication reconciliation might also reduce costs.

Objective:

To evaluate the effect of medication reconciliation on medication costs after hospital discharge in relation to hospital pharmacy labor costs.

Methods:

A prospective observational study was performed. Patients discharged from the pulmonology department were included. A pharmacy team assessed medication errors prevented by medication reconciliation. Interventions were classified into 3 categories: correcting hospital formulary-induced medication changes (eg, reinstating less costly generic drugs used before admission), optimizing pharmacotherapy (eg. discontinuing unnecessary laxative), and eliminating discrepancies (eg, restarting omitted preadmission medication). Because eliminating discrepancies does not represent real costs to society (before hospitalization, the patient was also using the medication), these medication costs were not included in the cost calculation. Medication costs at 1 month and 6 months after hospital discharge and the associated tabor costs were assessed using descriptive statistics and scenario analyses. For the 6-month extrapolation, only medication intended for chronic use was included.

Results:

Two hundred sixty-two patients were included. Correcting hospital formulary changes saved €1 63/patient (exchange rate: EUR 1 = USD 1.3443) in medication costs at 1 month after discharge and €9.79 at 6 months. Optimizing pharmacotherapy saved €20.13/patient in medication costs at 1 month and €86.86 at 6 months. The associated labor costs for performing medication reconciliation were €41.04/patient. Medication cost savings from correcting hospital formulary-induced changes and optimizing of pharmacotherapy (€96.65/patient) outweighed the labor costs at 6 months extrapolation by €55.62/patient (sensitivity analysis €37.25–71.10).

Conclusions:

Preventing medication errors through medication reconciliation results in higher benefits than the costs related to the net time investment.
Synthetic Cathinones (Bath Salts): Legal Status and Patterns of Abuse
Authors: Fass Jennifer A , Fass Andrea D , Garcia Angela S
Published: March 2012

Objective:

To review the current legal status and patterns of abuse of bath salts.

Data Sources:

A literature search was conducted through MEDLINE (1950-December 2011), PubMed (1966–December 2011), EMBASE (1966-December 2011), and International Pharmaceutical Abstracts (1970-December 2011) using the search terms bath salts, mephedrone, and methylenedioxypyrovalerone to identify articles on the legal status of bath salts and on studies focusing on patterns of abuse of bath salts. The GovTrack.us Web site was searched to determine the status of federal bills regarding bath salts. The National Association of Boards of Pharmacy and Drug Enforcement Administration Web sites and the Federal Registerwere also examined to identify legislation on bath salts.

Study Selection and Data Extraction:

Case reports and studies regarding bath salts were examined. Federal laws involving bath salts were also evaluated.

Data Synthesis:

The Department of Justice issued a final order in the Federal Register, temporarily placing the 3 synthetic stimulants, mephedrone, methylenedioxypyrovalerone, and methylone, under Schedule I of the Controlled Substances Act. Literature evaluated included case reports, retrospective studies, surveys, toxicology data, and chemical analyses studies. Information in the literature demonstrated that bath salts are highly abused, and common adverse effects include hypertension, tachycardia, and psychiatric symptoms.

Conclusions:

Psychoactive substances recently sold as bath salts have been placed in Schedule I of the Controlled Substances Act. Pharmacists can play an important role in raising awareness on the dangers of bath salts abuse through patient counseling and community outreach programs. The evidence on legal status and patterns of abuse clearly demonstrates that bath salts contain dangerous substances that should be permanently controlled.
Fluorescence Sensor for the Quantification of Unbound Bilirubin Concentrations
Authors: Huber Andrew H , Zhu Baolong , Kwan Thomas , Kampf J Patrick , Hegyi Thomas , Kleinfeld Alan M
Published: March 2012

BACKGROUND

Hyperbilirubinemia in jaundiced neonates is routinely assessed by use of total serum bilirubin. However, the unbound or free form (Bf), not total bilirubin, crosses the blood–brain barrier and can be neurotoxic. Although the peroxidase-mediated oxidation of bilirubin can be used to measure plasma concentrations of Bf, this measurement is relatively complex and the assay is not routinely used. We describe a fluorescence sensor for quantifying Bf in plasma.

METHODS

Our method uses a mutated fatty acid binding protein labeled with the fluorescent molecule acrylodan (BL22P1B11), whose fluorescence is quenched upon binding bilirubin. Another configuration (BL22P1B11-Rh) was developed that uses BL22P1B11 together with the fluorophore rhodamine B, which responds by a change in the ratio of its fluorescence.

RESULTS

The “Bf probes” were calibrated with aqueous solutions of bilirubin and yielded similar bilirubin dissociation constants [Kd = 16 (1.5) nmol/L]. We used the probes to determine Bf concentrations in equilibrium with human serum albumin (HSA) and in human plasma samples supplemented with bilirubin. We obtained equivalent Bf values in both systems, and the Bf probe results were in agreement with the peroxidase assay. Bf measurements revealed that bilirubin–HSA binding was well described by 2 sites with Kd values of 15.4 (1) nmol/L and 748 (14) nmol/L. We measured Bf concentrations in the range expected in jaundiced neonates with a mean CV of approximately 3%.

CONCLUSIONS

The BL22P1B11-Rh probe provides accurate plasma sample Bf concentrations with a single measurement, in 1 min with either a handheld Bf meter or a laboratory fluorometer.
New Products: The Antidote to Private Label Growth?
Authors: Gielens Katrijn
Published: March 2012

As private labels (PLs) continue to grow in power and market share, product innovation has become one of the strongest weapons in the national brand (NB) manufacturer's arsenal. In this article, the author assesses when and to what extent new products change NBs' market position. To address this question, more than 300 NB and PL introductions are analyzed using a multibreak model that quantifies the impact of product introductions on own share, rival NB and PL share, and category sales. Drawing on empirical generalizations, the author finds that products introduced by leading NBs, standard PLs, and premium PLs are more likely to increase category sales than products introduced by follower NBs or economy PLs. New products introduced by leader and follower NBs more often boost own share. Thus, new products help prevent the decline of NB shares. With respect to competitive impact, new products affect rival shares, with the exception of those launched by economy PLs. Still, NBs tend to hurt rival NBs more often than PLs, and only the leading NB is likely to steal share from all three PL tiers. Moreover, standard PLs tend to be harmed less often by rival new products, unless introduced by the leading NB. Overall, PLs are more likely to be affected by a NB that maintains a large price gap and offers new products with new intrinsic or usage benefits. To fight economy PLs successfully, however, NBs must maintain a smaller price gap, while offering products that focus less on intrinsic and usage benefits.
Gap-Junctional Coupling of Mammalian Rod Photoreceptors and Its Effect on Visual Detection
Authors: Li Peter H. , Verweij Jan , Long James H. , Schnapf Julie L.
Published: March 2012

The presence of gap junctions between rods in mammalian retina suggests a role for rod-rod coupling in human vision. Rod coupling is known to reduce response variability, but because junctional conductances are not known, the downstream effects on visual performance are uncertain. Here we assessed rod coupling in guinea pig retina by measuring: (1) the variability in responses to dim flashes, (2) Neurobiotin tracer coupling, and (3) junctional conductances. Results were consolidated into an electrical network model and a model of human psychophysical detection. Guinea pig rods form tracer pools of 1 to ∼20 rods, with junctional conductances averaging ∼350 pS. We calculate that coupling will reduce human dark-adapted sensitivity ∼10% by impairing the noise filtering of the synapse between rods and rod bipolar cells. However, coupling also mitigates synaptic saturation and is thus calculated to improve sensitivity when stimuli are spatially restricted or are superimposed over background illumination.
Neurofibromin Modulates Adult Hippocampal Neurogenesis and Behavioral Effects of Antidepressants
Authors: Li Yun , Li Yanjiao , McKay Renée M. , Riethmacher Dieter , Parada Luis F.
Published: March 2012

Neurogenesis persists in the rodent dentate gyrus (DG) throughout adulthood but declines with age and stress. Neural progenitor cells (NPCs) residing in the subgranular zone of the DG are regulated by an array of growth factors and respond to the microenvironment, adjusting their proliferation level to determine the rate of neurogenesis. Here we report that genetic deletion of neurofibromin (Nf1), a tumor suppressor with RAS-GAP activity, in adult NPCs enhanced DG proliferation and increased generation of new neurons in mice.Nf1loss-associated neurogenesis had the functional effect of enhancing behavioral responses to subchronic antidepressants and, over time, led to spontaneous antidepressive-like behaviors. Thus, our findings establish an important role for the Nf1-Ras pathway in regulating adult hippocampal neurogenesis, and demonstrate that activation of adult NPCs is sufficient to modulate depression- and anxiety-like behaviors.
Executive Control Over Cognition: Stronger and Earlier Rule-Based Modulation of Spatial Category Signals in Prefrontal Cortex Relative to Parietal Cortex
Authors: Goodwin Shikha J. , Blackman Rachael K. , Sakellaridi Sofia , Chafee Matthew V.
Published: March 2012

Human cognition is characterized by flexibility, the ability to select not only which action but which cognitive process to engage to best achieve the current behavioral objective. The ability to tailor information processing in the brain to rules, goals, or context is typically referred to as executive control, and although there is consensus that prefrontal cortex is importantly involved, at present we have an incomplete understanding of how computational flexibility is implemented at the level of prefrontal neurons and networks. To better understand the neural mechanisms of computational flexibility, we simultaneously recorded the electrical activity of groups of single neurons within prefrontal and posterior parietal cortex of monkeys performing a task that required executive control of spatial cognitive processing. In this task, monkeys applied different spatial categorization rules to reassign the same set of visual stimuli to alternative categories on a trial-by-trial basis. We found that single neurons were activated to represent spatially defined categories in a manner that was rule dependent, providing a physiological signature of a cognitive process that was implemented under executive control. We found also that neural signals coding rule-dependent categories were distributed between the parietal and prefrontal cortex—however, not equally. Rule-dependent category signals were stronger, more powerfully modulated by the rule, and earlier to emerge in prefrontal cortex relative to parietal cortex. This suggests that prefrontal cortex may initiate the switch in neural representation at a network level that is important for computational flexibility.
Vocal Exploration Is Locally Regulated during Song Learning
Authors: Ravbar Primoz , Lipkind Dina , Parra Lucas C. , Tchernichovski Ofer
Published: March 2012

Exploratory variability is essential for sensorimotor learning, but it is not known how and at what timescales it is regulated. We manipulated song learning in zebra finches to experimentally control the requirements for vocal exploration in different parts of their song. We first trained birds to perform a one-syllable song, and once they mastered it, we added a new syllable to the song model. Remarkably, when practicing the modified song, birds rapidly alternated between high and low acoustic variability to confine vocal exploration to the newly added syllable. Furthermore, even within syllables, acoustic variability changed independently across song elements that were only milliseconds apart. Analysis of the entire vocal output during learning revealed that the variability of each song element decreased as it approached the target, correlating with momentary local distance from the target and less so with the overall distance within a syllable. We conclude that vocal error is computed locally in subsyllabic timescales and that song elements can be learned and crystallized independently. Songbirds have dedicated brain circuitry for vocal babbling in the anterior forebrain pathway (AFP), which generates exploratory song patterns that drive premotor neurons at the song nucleus RA. We hypothesize that either AFP adjusts the gain of vocal exploration in fine timescales or that the sensitivity of RA premotor neurons to AFP/HVC inputs varies across song elements.
Mechanisms of Taste Bud Cell Loss after Head and Neck Irradiation
Authors: Nguyen Ha M. , Reyland Mary E. , Barlow Linda A.
Published: March 2012

Taste loss in human patients following radiotherapy for head and neck cancer is a common and significant problem, but the cellular mechanisms underlying this loss are not understood. Taste stimuli are transduced by receptor cells within taste buds, and like epidermal cells, taste cells are regularly replaced throughout adult life. This renewal relies on progenitor cells adjacent to taste buds, which continually supply new cells to each bud. Here we treated adult mice with a single 8 Gy dose of x-ray irradiation to the head and neck, and analyzed taste epithelium at 1–21 d postirradiation (dpi). We found irradiation targets the taste progenitor cells, which undergo cell cycle arrest (1–3 dpi) and apoptosis (within 1 dpi). Taste progenitors resume proliferation at 5–7 dpi, with the proportion of cells in S and M phase exceeding control levels at 5–6 and 6 dpi, respectively, suggesting that proliferation is accelerated and/or synchronized following radiation damage. Using 5-bromo-2-deoxyuridine birthdating to identify newborn cells, we found that the decreased proliferation following irradiation reduces the influx of cells at 1–2 dpi, while the robust proliferation detected at 6 dpi accelerates entry of new cells into taste buds. In contrast, the number of differentiated taste cells was not significantly reduced until 7 dpi. These data suggest a model where continued natural taste cell death, paired with temporary interruption of cell replacement, underlies taste loss after irradiation.
Gene Expression Profiling of Neural Stem Cells and Their Neuronal Progeny Reveals IGF2 as a Regulator of Adult Hippocampal Neurogenesis
Authors: Bracko Oliver , Singer Tatjana , Aigner Stefan , Knobloch Marlen , Winner Beate , Ray Jasodhara , Clemenson Gregory D. , Suh Hoonkyo , Couillard-Despres Sebastien , Aigner Ludwig , Gage Fred H. , Jessberger Sebastian
Published: March 2012

Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentate gyrus (DG). How gene expression signatures differ among NSCs and immature neurons remains largely unknown. We isolated NSCs and their progeny in the adult DG using transgenic mice expressing a GFP reporter under the control of theSox2promoter (labeling NSCs) and transgenic mice expressing a DsRed reporter under the control of thedoublecortin(DCX) promoter (labeling immature neurons). Transcriptome analyses revealed distinct gene expression profiles between NSCs and immature neurons. Among the genes that were expressed at significantly higher levels in DG NSCs than in immature neurons was the growth factor insulin-like growth factor 2 (IGF2). We show that IGF2 selectively controls proliferation of DG NSCsin vitroandin vivothrough AKT-dependent signaling. Thus, by gene expression profiling of NSCs and their progeny, we have identified IGF2 as a novel regulator of adult neurogenesis.
Rodents Rely on Merkel Cells for Texture Discrimination Tasks
Authors: Maricich Stephen M. , Morrison Kristin M. , Mathes Erin L. , Brewer Brittany M.
Published: March 2012

The cutaneous somatosensory system contains multiple types of mechanoreceptors that detect different mechanical stimuli (Johnson, 2001). These stimuli, either alone or in combination, are ultimately interpreted by the brain as different aspects of the sense of touch. Psychophysical and electrophysiological experiments in humans and other mammals implicate one of these mechanoreceptors, the Merkel cell/neurite complex, in two-point discrimination and the detection of curvature, shape, and texture (Johnson and Lamb, 1981; Johnson et al., 2000; Johnson, 2001). However, whether Merkel cell/neurite complex function is required for the detection of these stimuli is unknown. We genetically engineered mice that lack Merkel cells (Maricich et al., 2009; Morrison et al., 2009) to directly test the hypothesis that Merkel cell/neurite complexes are necessary to perform these types of sensory discrimination tasks. We found that mice devoid of Merkel cells could not detect textured surfaces with their feet while other measures of motor and sensory function were unaffected. Interestingly, these mice retained the ability to discriminate both texture and shape using their whiskers, suggesting that other somatosensory afferents can functionally substitute for Merkel cell/neurite complexes in this sensory organ. These findings suggest that Merkel cell/neurite complexes are essential for texture discrimination tasks involving glabrous skin but not whiskers.
Neural Reactivation Reveals Mechanisms for Updating Memory
Authors: Kuhl Brice A. , Bainbridge Wilma A. , Chun Marvin M.
Published: March 2012

Our ability to remember new information is often compromised by competition from prior learning, leading to many instances of forgetting. One of the challenges in studying why these lapses occur and how they can be prevented is that it is methodologically difficult to “see” competition between memories as it occurs. Here, we used multi-voxel pattern analysis of human fMRI data to measure the neural reactivation of both older (competing) and newer (target) memories during individual attempts to retrieve newer memories. Of central interest was the following: (1) whether older memories were reactivated during retrieval of newer memories; (2) how reactivation of older memories related to retrieval performance; and (3) whether neural mechanisms engaged during the encoding of newer memories were predictive of neural competition experienced during retrieval. Our results indicate that older and newer visual memories were often simultaneously reactivated in ventral temporal cortex—even when target memories were successfully retrieved. Importantly, stronger reactivation of older memories was associated with less accurate retrieval of newer memories, slower mnemonic decisions, and increased activity in anterior cingulate cortex. Finally, greater activity in the inferior frontal gyrus during the encoding of newer memories (memory updating) predicted lower competition in ventral temporal cortex during subsequent retrieval. Together, these results provide novel insight into how older memories compete with newer memories and specify neural mechanisms that allow competition to be overcome and memories to be updated.